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andre röhner

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Andrea Gonzalez Caballero Guitar Technics and Music - Rondeña by R. Sainz de la Maza

Chapkin, Robert S. Two of the most abundant bioactive lipids enriched in fish oil, eicosapentaenoic acid EPA, n-3 and docosahexaenoic acid DHA, n-3 are capable of altering cell membrane properties and resident protein activity.

Recent evidence suggests that DHA can perturb specialized regions of the plasma membrane known as lipid rafts.

Lipid rafts are mesoscale nm , heterogeneous microdomains that are enriched in cholesterol, sphingolipids, polyphosphoinositides and saturated acyl chains.

DHA is sterically incompatible with cholesterol, which can contribute to the disruption of lipid rafts. This is noteworthy, because lipid rafts serve as signaling platforms by compartmentalizing plasma membrane proteins and lipids.

In response to stimuli, nanometer-scale domains can coalesce and display high molecular order.

Many of these lipid raft mediated processes, e. Additionally, chronic inflammation, central to the process of tumorigenesis, involves excessive cell activation, which is in part regulated by lipid rafts.

Since AA-derived eicosanoids, e. However, due to safety concerns surrounding the use of pharmaceutical agents designed to target Ptgs2 cyclooxygenase II and its downstream targets, it is important to identify new targets upstream of Ptgs2.

Therefore, we determined the utility of antagonizing membrane AA levels as a novel approach to suppressing AA-derived eicosanoids.

Overall, the knowledge obtained from mechanistic studies targeting cell membranes will provide a solid underpinning for the role of dietary lipids in the resolution of chronic inflammation and cancer prevention.

This large superfamily of heptahelical molecules comprises receptors for dopamine, serotonin, epinephrine, opioids, and cannabinoids, just to mention a few.

The proper function of GPCR is critical for all higher forms of life. We are conducting structural and functional studies on two reconstituted GPCR of class A, bovine rhodopsin and recombinant cannabinoid CB2 receptor.

The GPCR are investigated at close to functional conditions, in a fluid lipid matrix with a biologically relevant composition of lipids.

Our studies place particular emphasis on polyunsaturated lipids as found in brain. The lipid matrix both preserves structural integrity of GPCR and enhances or prevents transition into the state of the receptor that activates G protein.

I will report on adjustments of the lipid matrix to the presence of the receptor and on the influence of receptor function from lipid headgroups and hydrocarbon chains.

The composition of the lipid matrix is, perhaps, the most important allosteric modulator of GPCR function.

I will also address opportunities to study receptor structure in the lipid matrix at close to functional conditions by solid state NMR.

Cardiac Metabolism, University of Maastricht, Netherlands Transport of fatty acids is regulated by membrane fatty acid transporters, e.

In recent years common genetic variants of these proteins have been identified and were found to associate with circulating lipid profiles and metabolic phenotypes.

For instance, subjects with CD36 gene variants that result in a lower CD36 expression level were found to be less susceptible to the metabolic complications of obesity.

Likewise, common variants of the liver-type FABP were reported to influence insulin resistance and type 2 diabetes. In view of the still emerging functions of these fatty acid-binding proteins, such as the role of CD36 in fat taste perception and that of CD36 and cytoplasmic FABPs in lipid signal transduction and inflammation, common gene variants are expected to contribute to individual variability in these parameters.

These new developments as well as our current understanding of the underlying molecular mechanisms will be discussed in this lecture.

Division of Metabolism, Endocrinology and Nutrition, Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, WA The accumulation of cholesterol by artery wall macrophages plays a critical role in atherosclerosis, the leading cause of cardiovascular disease.

HDL has been proposed to become dysfunctional in subjects with atherosclerosis, but the underlying mechanisms are poorly understood.

One potential pathway involves myeloperoxidase MPO , a potent source of reactive intermediates in human artery wall macrophages.

We used mass spectrometry to demonstrate that apoA-I of HDL isolated from patients established heart disease exhibits site-specific chlorination of tyrosine, a characteristic product of MPO.

University of British Columbia, Canada During stroke, neurons that are deprived of their normal substrates can show signs of structural damage to dendrites after as little as 2 min of ischemia.

Mitochondria also become depolarized within minutes after ishcemia. Mitochondrial dysfunction and the opening of the mitochondrial permeability transition pore mPTP are proposed to link ischemic ionic imbalance to mitochondrially mediated cell death pathways.

Some neurons escape damage within the penumbra. Over time weeks , surviving brain tissue is thought to compensate for regions lost to stroke.

It is generally assumed that recovery is a process that occurs over weeks and involves both the formation of new structural circuits and the alternative use of spared circuits.

Recovery after a small stroke may involve spared peri-infarct tissue with function similar to the infarct. In contrast, after a large stroke, tissue with similar function may only be found at more distant sites or regions within the unaffected contralateral hemisphere where structural remodeling can be observed.

Using a large bilateral craniotomy preparation in mouse, we show that targeted ischemia to even a single arteriole causes alterations in the patterns of sensory-evoked activity that extend beyond peri-infarct areas into somatotopic regions of the unaffected hemisphere as early as 30 min after stroke onset.

These findings suggest that existing sensory pathways are capable of redistributing activity to even the contralateral hemisphere.

To assess changes in functional connectivity after stroke, we are developing an automated approach to monitor intrahemispheric and interhemispheric functional relationships by the activation of Channelrhodopsin-2 ChR2 -expressing cortical neurons at arbitrary cortical points in transgenic mice.

To monitor regional cortical activity we employ organic voltage sensitive dyes. We extend the point stimulation to areas targeting association cortices and secondary somatosensory regions that are inaccessible to direct stimulation via the senses and could potentially contribute to reorganized circuitry.

We apply graph theory and complex network analysis to connection matrices derived from these functional maps to elucidate reciprocal connections between primary and secondary sensory areas, identify network hubs, and determine asymmetries in intracortical connectivity.

We anticipate that new approaches to both monitor and manipulate neuronal function will be important to describe how spared cortical circuits compensate for brain tissue lost to stroke.

M; Maggie Strable Departments of Biochemistry and of Nutritional Sciences, University of Wisconsin-Madison, Madison Wisconsin, USA Dietary fatty acids or fatty acids synthesized de novo in conjunction with nuclear receptors and transcription factors affect the transcription of a variety of genes.

The mechanisms by which these interactions and consequent effects of the individual class of fatty acids occur is proving to be complicated and yet it is invaluable to our understanding of the role that dietary fat can play in disease management and prevention.

We have used the stearoyl-CoA desaturase SCD mouse model to investigate the role of de novo synthesized fatty acids in the regulation of lipogenic gene expression.

Past work demonstrated that SCD1 deficiency impairs hepatic lipogenesis and protects against diet-induced obesity. To address this, we produced liver-specific transgenic mice expressing human SCD5, which preferentially synthesizes oleate n-9 , and introduced this transgene into GKO mice.

Hepatic oleate synthesis increased plasma glucose levels and largely prevented very-low-fat diet-induced weight loss.

This work suggests that hepatic MUFA are involved in regulation of lipogenesis and gluconeogenesis. Supported by NIH. Within a single generation populations that once were the focus of remedial supplementation programmes aimed at preventing malnutrition are now the focus of anti-obesity campaigns.

Many countries have passed through the 'nutrition transition' and others are rapidly progressing.

The desirability, affordability and abundance of refined vegetable oils has resulted in major changes in fat intake as a proportion of energy.

The quality and type of oils is highly variable and may be having profound health effects that have yet to be properly explored.

Despite this progress in many nations there remain large swathes of poverty where fat intakes may be marginal; creating a low-energy density in diets that compromises children's ability to ingest sufficient energy and potentially impairing the absorption of fat-soluble vitamins.

Essential fatty acid intakes are frequently compromised in pregnancy and young childhood, though there is great heterogeneity among studies.

Some of this heterogeneity may be caused by methodological issues, particularly in respect of accurately assaying the minor components of fatty acid profiles such as the long-chain PUFAs, and international ecological studies using standardised methodologies would be highly desirable.

Lipid-based nutrient supplements LNS provide a particularly suitable vehicle for enhancing the essential fatty acid itakes of the most at-risk mothers and children and the many on-going research challenges will be summarised.

The Role of Highly Unsaturated Fatty Acids in the Health and Disease of the Retina SanGiovanni, John Paul NEI,National Institutes of Health, USA The presentation will include: 1 an overview of extant work characterizing the capacity of diet-based fatty acids, their precursors, and metabolites to alter retinal structure and function; 2 discussion of a genomic systems-based approach to investigate relationship of receptors, transporters, enzymes and hormones impacting or impacted by these molecules in the context of pathogenesis of eye diseases manifesting neovascular and neurodegenerative components; and, 3 commentary on promising venues for development of preventive and therapeutic applications identified via the systems-based approach.

New endogenous mechanisms involved in the resolution of acute self-limited inflammatory exudates have provided insight into the control of both host defense and local acute inflammation.

Using a systems approach coupled with lipid mediator LM -metabololipidomics that we introduced, permitted the identification of several new families of potent local acting bioactive lipid-derived mediators in resolving exudates CN Serhan et al Nature Immunology This presentation shall update new advances on the biosynthesis and functions of the founding members of this novel genus of specialized pro-resolving mediators SPM and their roles as agonists of resolution.

The SPM include 3 families of chemical mediators: resolvins, protectins and the most recent addition, maresins from macrophages.

These are local autacoids biosynthesized in resolving exudates from essential omega-3 fatty acids n-3, EPA and DHA that possess potent multi-pronged anti-inflammatory, pro-resolving, reduce pain and microbial clearance actions in animal models.

Low dose aspirin also triggers production of endogenous chiral epimers from certain of SPM pathways that have to be proven bioactive and stimulate resolution.

Many other research groups worldwide now confirm endogenous formation of resolvins and protectins and their organ-protective roles and the first Rv is currently in human clinical trial.

For example, SPM have potent actions in murine ischemic renal injury, obesity-induced insulin resistance and liver disease, murine colitis and arthritis, as well as reducing pain.

These findings change the old concept that resolution of inflammation is a passive process. Together, they indicate that natural resolution pathways may underlie many prevalent diseases associated with uncontrolled inflammation and open the potential for resolutionbased therapeutics.

Triglyceride Digestion and Transport Tso, Patrick The focus of my talk will be on the digestion and absorption of dietary biliary lipids in the gastrointestinal tract, and the physiology of this event.

The digestion of dietary triacylglycerol TG begins in the stomach and continues in the intestinal lumen.

Both gastric lipase and pancreatic lipase contribute to its digestion. Following this initial breakdown of dietary TG, the hydrolytic products, monoacylglycerols MG and fatty acids FA , are solubilized in micelles and taken into the enterocyte by both passive as well as carrier mediated processes.

The importance of the unstirred water layer to the uptake of TG digestion products, as proposed by Dr. John Dietschy, will be described.

I will also focus on the uptake of cholesterol by the enterocytes, via the NPC1L1 transporter. Following uptake into the enterocute, MG and FA are transported from the apical membrane to the endoplasmic reticulum, and re-esterified to form TG involving various enzymes.

I will also focus on the mechanism of chylomicron formation in the enterocytes, and the role of the microsomal triglyceride transfer protein in regulating the process of chylomicron formation.

Additionally, the trafficking of chylomicron particles from the endoplasmic reticulum to the Golgi apparatus will be described, as well as the process of chylomicron exocytosis and how they journey to the lacteals.

I plan to conclude the talk with a discussion of the role of various apolipoproteins in intestinal lipid transport by the enterocytes and how the conscious lymph fistula mouse model has contributed to our knowledge of the subject.

This lecture will examine the relationship between fatty acid composition and immune function, evaluate the influence of ageing on responsiveness of the immune system to n-3 polyunsaturated fatty acids PUFA , describe the role of lipid rafts in immunomodulation by fatty acids, highlight advances in eicosanoid biology, and describe emerging receptors as targets for action by fatty acids.

Hess, Manabu T. Among the most critical developments in this process is the biogenesis of an organelle unique to sperm, the acrosome, whose construction is dependent on stage-specific vesicular trafficking and membrane fusion events.

Deficiency in docosahexaenoic acid DHA was recently shown to result in a failure of acrosome biogenesis; however a role for DHA in membrane fusion has yet to be defined.

Similarly, we show by immunohistochemistry that the intracellular localization of acrosin a cargo protein of proacrosomal vesicles is normally distributed in early Golgi-phase spermatids, but in subsequent phases of spermiogenesis is dispersed throughout the cytosol in an abnormal punctate pattern.

Further, membrane fusion proteins syntaxin2 and VAMP4 displayed aberrant accumulation throughout spermiogenesis; and endoplasmic reticulum cisternae, as well as smaller transport vesicles, were present in excess on the cis-face of the Golgi, each suggestive of impaired intracellular transport or fusion.

Modulation of normal rat colon mucosa highlighted the differential effects of fish and borage oils on certain lipid and FA parameters.

ACF formation was significantly enhanced by fish oil, whereas borage oil counteracted this effect. However, the efficacy of the intervention appears to be determined by the respective stage in carcinogenesis.

S, and Anderson R. We used a skin-specific promoter to drive the expression of ELOVL4 protein thereby generating animals with global Elolvl4 deletion except in the skin.

The skin rescued mice are runts, have defects in eyelid opening, and die within the first three weeks from birth. This regulation extends to the sub-cellular compartments that make up the cellular architecture.

Moreover, lipids help recruit proteins to specific locations and maintain their function. Determining spatiality at the subcellular level how the lipid composition varies is therefore very important in terms of understanding the role sub-cellular compartmentation plays in regulating cellular metabolism.

To demonstrate this approach this study reports a comprehensive analysis of the subcellular proteome and lipidome of a hepatoma cell line FaO and its utility for monitoring sub-cellular changes associated with Non-Genotoxic Carcinogens NGCs exemplified by Mono 2-ethylhexyl phthalate MEHP.

A self-generating density gradient was used to partially separate organelles into individual fractions. Fractions were selected based on their profile of proteins, measured by western blotting.

Distributions were then determined by isobaric mass tagging, LC-MS and multivariate data analysis, based on proteins with known organelle locations.

This analysis of enriched organelle fractions identified numerous lipid species, whose type and concentration varied between different organelles.

Following MEHP treatment, changes were seen in the observed distribution and concentration of the lipids including PtdEtn and PtdIns throughout the gradient, supporting the hypothesis that the some of the changes in the lipid profiles, due to NGCs, are a result of induced organelle proliferation.

Here we present a rapid few seconds , real time method to analyze the fatty acid profiles in food and biological samples. To illustrate the potential of this approach we analyzed lipid profiles of edible oils e.

Samples were swiped on a capillary and placed near the mass spectrometer ion source. Lipids were ionizated by DART, separated by ion mobility msec and mass analyzed by the time-of-flight mass analyzer.

This generated 3D maps drift time, exact mass, and intensity of the sample composition at the molecular level. Our approach of analysis is suitable for the rapid screening of various bioactive lipids, e.

Potential applications include fingerprinting of biological phenotypes and comparative lipidomic analysis in the areas of personalized medicine, disease diagnostics and food analysis.

Consumption of a diet high in saturated- and trans- fatty acids increases risk of cardiovascular disease. However, consumption of the dietary trans fatty acids conjugated linoleic acids CLA may protect against cardiovascular disease and improve platelet function.

Many issues relating to the potential mechanism of protection are unknown. Platelet proteins from washed human platelets were separated in a total of protein spots using 2-dimensional gel electrophoresis.

Pathway analysis based on KEGG pathways revealed that the majority of these proteins was involved in regulation of the cytoskeleton and platelet structure, or receptor activity, signalling and focal adhesion.

These proteins, or indeed downstream proteins or metabolites, could be candidate biomarkers to measure the efficacy of fatty acids on platelet function in future nutritional intervention studies.

In the present study we fed Zucker rats with 0. In addition, the decreased ratio was associated to a lower deposition of ectopic fat in liver and heart, plasma NEFA, glycemia and insulin resistance.

We may conclude that endocannabinoid balance between visceral and subcutaneous adipose tissues is crucial for body fat homeostasis and low doses of dietary n-3PC are able to affect significantly this balance and significantly improve metabolic syndrome in obese zucker rats.

University of Western Australia, Australia Background: Overweight people are at risk of developing heart disease due to their predisposition of also having high blood pressure, lipids and glucose levels.

The cytochrome P metabolites of arachidonic acid are important regulators of vascular function and homeostasis.

This study examined metabolism of arachidonic acid by the cytochrome P epoxygenase that leads to formation of 4 epoxyeicosatrienoic acid EET regioisomers.

EETs are vasodilators, and inhibit platelet aggregation. Their actions are attenuated by metabolism to dihydroxyeicosatrianoic acids DHETs by soluble epoxide hydrolase.

Their possible contribution to cardiovascular risk has not been assessed in overweight humans. Results: The volunteers were aged Plasma DHETs were not different between the groups Platelet DHETs were not different between the groups 0.

Conclusions: The increase in plasma EETs in the MetS may be a homeostatic response to elevated blood pressure or increased circulating vasoconstrictors that have been linked to insulin resistance in these subjects.

The reduced platelet EETs levels may be of relevance to increased platelet reactivity and aspirin resistance that has been described in subjects with the metabolic syndrome.

Litmanovitz, K. Davidson, A. Eliakim, R. Regev, T. Dolfin, Y. Lifshitz, D. Contrary, palmitic-acid in the sn-1 and sn-3 positions, the predominantly fat composition in regular infant formulas, is hydrolyzed by pancreatic lipase, resulting in free palmitic-acid that forms poorly absorbed complexes with calcium, also associated with lower bones calcium deposition and abdominal discomfort.

Anthropometrics and bone SOS by quantitative ultrasound Sunlight Omnisense were measured at randomization, and at 6 and 12 weeks postnatal.

Before each visit parents filled a three days report on infant feeding, stool characteristics and crying.

Results: There were no significant differences in anthropometrics at randomization and at 12 weeks postnatal. Infants in the InFat group had less episodes of crying per day and significant decrease in daily crying compared to Control group.

Conclusion: The consumption of InFat formula by term infants for 12 weeks had beneficial effects on bone SOS compared to regular Control formula and was most similar to the breastfed group.

Pipingas, A. Z Ament, Z. Swinburne University of Technology, Melbourne, Australia Background: Recent evidence suggests that, although only present in low quantities in the brain, eicosapentaenoic acids omega-3 fatty acid EPA , enhances early visual cortical processing measured with multifocal visual evoked potentials Bauer et al.

However, while docosahexaenoic omega-3 fatty acid DHA has been shown to increase neural activity during a sustained visual attention task McNamara et al.

Supplementations were administered using a double-blind, crossover design, with a day washout period between the two supplementation periods.

Participants were scanned at Baseline prior to supplementation , and after each day supplementation period.

Reaction times and response accuracy were recorded. Results: The EPA-rich supplementation was associated with a reduction in functional activation in the anterior cingulate cortex ACC when compared to Baseline.

Conclusions: Reduced brain functional activation, coupled with faster reaction times during a Stroop Color Word Interference Task suggests a mechanism of improved neural efficiency following a day EPA-rich supplementation.

Effects of iron and n-3 fatty acid supplementation, alone and in combination, on cognition: a randomized, double-blind, placebo controlled intervention in iron-deficient South African school children Baumgartner, Jeannine; CM Smuts, L Malan, MB Zimmermann Centre of Excellence in Nutrition, North-West University, Potchefstroom, South Africa; Laboratory of Human Nutrition, Institute of Food, Nutrition and Health, Switzerland Background: Little is known about the combined effects of iron and n-3 fatty acid n-3 FA supplementation in children suffering from both deficiencies.

Objective: We investigated whether providing iron and a mixture of docosahexaenoic DHA and eicosapentaenoic acid EPA , alone and in combination, to children with iron deficiency and poor n-3 FA intakes will improve cognitive performance.

No effects on cognition were found in the non-anaemic children. Conclusions: Our findings suggest that iron supplementation may improve verbal and non-verbal learning and memory in children suffering from anaemia.

Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, School of Medicine, USA The significance of the selective enrichment in omega-3 essential fatty acids in the nervous system has remained, until recently, incompletely understood.

We found that NPD1 is promptly made in response to oxidative stress and brain ischemia-reperfusion, and in the presence of neurotrophins.

We will present the following studies: 1 DHA i. Neurological function was evaluated on up to 7 days after MCAo.

DHA improved behavioral scores and reduced cortical , subcortical and total infarct volumes 7 days after stroke. In addition, DHA reduced microglia infiltration and increased number of astrocytes and neurons.

Then we performed the total chemical synthesis of this molecule and tested the novel AT-NPD1 by iv 1 hr after 2h middle cerebral artery occlusion in rats.

Brain edema, computed from T2WI in the cortex penumbra and striatum core , was elevated in the saline group. In conclusion NPD1 targets neuroinflammatory signaling at various check points as well as modulates apoptotic cascades and other forms of cell death in turn promoting homeostatic regulation of neuronal circuitry integrity in experimental stroke.

In this talk, I will review how polyunsaturated fatty acids PUFA enter the brain, and the mechanisms that regulate their concentrations within brain phospholipids.

Whereas little evidence exists to support the incorporation of PUFA from lipoproteins into the brain, the incorporation rates of arachidonic and docosahexaenoic acid from the plasma unesterified pool into brain phospholipids closely approximate independent measures of their consumption rates by the brain.

Thus, with the use of radiolabelled fatty acids, it is possible to image and quantify their entry and uptake into the brain in rodents and, with positron emission tomography, in humans.

Upon entry into the brain, certain PUFA are highly conserved with extensive recycling within phospholipids, whereas others, such as eicosapentaenoic acid, are rapidly and extensively removed from the brain, in part, due to b-oxidation.

Identifying the mechanisms by which PUFA enter and are handled within the brain could lead to a better understanding of nutritional requirements for the brain as well as new therapeutic targets and novel imaging methods.

Background: Membrane phospholipid metabolism and redox regulation may be disturbed in schizophrenia. This has entailed randomised controlled trials with either omega-3 fatty acids or redox regulators.

The present study examines the effects of combining these agents. We hypothesized that lower baseline levels of polyunsaturated fatty acids PUFA would predict more benefit from trial drugs.

Patients aged years with DSM-IV schizophrenia, schizoaffective or schizophreniform disorders were consecutively included at admission to hospital.

Results: Ninety-nine patients were included. At baseline, erythrocyte PUFA were measured in 97 subjects. PUFA were bimodally distributed low, high.

Trial drugs had clinical effects beyond psychotic symptoms, mainly in low PUFA patients. When these agents are combined, they seem safe.

Diets rich in long-chain w-3 polyunsaturated fatty acids, namely docosahexaenoic acid DHA and eicosapentaenoic acid EPA , have been shown to have many beneficial effects such as the improvement of insulin sensitivity with beneficial effects against obesity and the prevention of cardiovascular diseases.

The content and the expression of adiponectin in adipose tissues were also measured 2 to evaluate the effects of DHA and EPA and their respective oxygenated metabolites on adiponectin secretion by 3T3-L1 adipocytes.

In all three white adipose tissues subcutaneous, epididymal and retroperitoneal tissues , the adipokine content was not significantly different between mice fed the w-3 polyunsaturated fatty acid-rich diet and mice fed with the standard diet.

However, the adiponectin content was dependent on adipose tissue depot. Adiponectin gene expression was significantly increased in epididymal and subcutaneous tissues of DHA-fed mice compared to control mice.

Our studies show that DHA and EPA rapidly improved the profile of secreted adiponectin in mice and in 3T3-L1 adipocytes and suggest that this effect may be mediated by their respective oxygenated metabolites.

These data confirm that dietary intake of w-3 polyunsaturated fatty acids may be beneficial for prevention or treatment of cardiovascular and obesity-associated diseases.

Myristoylated and palmitoylated proteins in the regulation of apoptosis and metabolism revealed through proteomic Berthiaume, Luc G; Dale D.

Martin, Morris A. Kostiuk, Megan C. Yap and Erwan Beauchamp Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Canada Fatty acylation, the attachment of fatty acids to proteins, is a critical mechanism of cellular control.

It impacts virtually every aspect of cellular life. Using chemical biology, we and others recently developed approaches leading to the rapid detection, identification and characterization of acylated proteins using azido- and alkynyl fatty acid analogs.

Myristoylation is the co- or post-translational attachment of myristate to N-terminal glycine residues of proteins.

Very little is known about post-translational myristoylation and our new characterization efforts resulted in the demonstration that 15 or more post-translationally myristoylated proteins exist in various cell lines undergoing apoptosis and in the identification of 5 of these with life and death implications for the cell.

Palmitoylation, the modification of proteins by palmitate, is known as a key membrane tethering and cellular localization mechanism.

In addition, we recently identified 21 palmitoylated proteins in mitochondria, where palmitoylation had various and profound effects on the catalytic activity and function of the modified proteins, with new implications in the regulation of metabolism.

In summary, we will present several examples illustrating how chemical biology approaches using click chemistry can catalyze the discovery of new roles for fatty acids in the regulation of cell death mechanisms and metabolism.

Objective: To investigate the association between levels of polyunsaturated fatty acids PUFA in maternal whole blood at week 24 of gestation and multiple lifestyle factors.

Data on socioeconomic and lifestyle factors was obtained prospectively during visits to the research unit, and fatty acid compositions of whole blood were determined.

Covariates that were significantly associated with the dependent variable in the univariate analyses were included in a stepwise backwards elimination multivariate model with a cut-off P-value of 0.

Results: We found independent positive significant associations between all n-3 PUFA variables and high education, high income, non-smoking, and being primiparious.

The n-6 PUFA variables were not associated with any of the factors. None of the preselected PUFA variables were associated with maternal age and asthma, urban living, or gender of the child.

Thus, when analyzing associations between n-3 PUFAstatus and health, the socioeconomic and lifestyle factors that have an independent association with both blood fatty acid composition and health must be taken into consideration.

Whale blubber was part of the traditional Eskimo diet. After news ads and telephone screening, participants were assessed for inclusion by a doctor.

Marine omega-3 fatty acid intake was restricted in a two week run-in period and during the 6 week intervention period.

Urinary F2 isoprostanes were generally low though significantly increased in WO group after 6 weeks, but not compared with FO group.

In conclusion; whale oil may possibly be as good an omega-3 source as fish oil, when given in equivalent medium dosage in the present short-term bioavailability study in healthy volunteers with a relatively high baseline omega-3 intake.

Information on source is uniquely retained by intrinsic stable isotope ratios, while kinetics and pool characteristics can be obtained starting with a specific enriched compound and following the transfer of label to products.

Most food plants operate with the C3 pathway, with corn using the C4 pathway. The acetate pool in animal cells has input from all sources of dietary carbon and thus reflects the mix of C3 and C4 plants in the diet.

Three examples will be presented. Carbon isotope analysis reveals that the major retinal saturated and monounsaturated fatty acids originate with corn, while DHA and n-3 both originate with C3 plants that were likely to be incidental feed components.

Steroid hormones and their metabolites reflect the dietary mix of C3 and C4 plants, with input from preformed dietary cholesterol.

These techniques were instrumental in establishing the biosynthetic efficiency for the conversion of precursor PUFA linoleic and linolenic acids to highly unsaturated fatty acids in pregnant and neonate non-human primates and humans.

Diets of the treatment groups were supplemented with chia or flax after 8 wk on H diet for a further 8 wk. Compared to the H rats, ALA-supplemented rats had improved insulin sensitivity and glucose tolerance, reduced visceral adiposity, decreased hepatic steatosis, reduced cardiac and hepatic inflammation and fibrosis without changes in plasma lipids or blood pressure.

Stearoyl-CoA desaturase-1 inhibition was shown as an increase in the substrate concentrations together with depletion of products in the heart, liver and the adipose tissue of ALA-supplemented rats.

The Ctrans-7 was preferentially stored in the adipose tissue; the relatively inert Cn-9 was stored in sensitive organs such as liver and heart and Cn-6, the parent fatty acid of the n-6 pathway, was preferentially metabolised.

Thus, ALA induces lipid redistribution associated with cardioprotection and hepatoprotection following reduced inflammatory cell infiltration.

These results strongly suggest that ALA produces pharmacological responses independent of conversion to longer chain fatty acids in inflammatory conditions such as metabolic syndrome and arthritis.

Design and methods: In an open-label randomized, controlled trial, healthy pregnant women either received a dietary intervention [supplementation with mg n-3 LCPUFAs per day and a dietary counseling to reduce AA intake] from 15th week of gestation until 4 months of lactation or followed their habitual diet.

Breastmilk fatty acid profile was analysed at 6 weeks and 4 months postpartum. Multiple regression models adjusting for relevant confounders were performed to determine the relationship between breastmilk fatty acid composition and infant fat mass assessed by skinfold thickness measurements and abdominal sonography up to 1 year pp.

AA content was comparable between both groups. Conclusion: Breastmilk n-3 fatty acids appear to stimulate fat mass growth over the 1st year of life whereas AA seems to be involved in the regulation of overall growth especially in the early postpartum period.

Individuals with type 2 diabetes are at high risk for cardiovascular events. Eicosapentaenoic acid EPA -derived resolvin lipid mediators have been shown to decrease platelet activation in ex-vivo human samples.

Platelet spreading, platelet granulate content release, and platelet receptor conformational changes are all correlated with increased cardiovascular disease.

When compared to untreated controls, there was a significant decrease in the percentage of spread platelets after treatment with increasing concentrations of 17R-resolvin D1, untreated A significant decrease in spreading was also observed when both 17 R and 17S-resolvin D1 were used in combination, untreated Our results suggest that DHA-derived resolvin lipid mediators have modest anti-platelet effects as quantified by platelet cell surface markers of activation and morphological spreading evaluation in individuals with and without type 2 diabetes.

More studies should be conducted to elucidate additional anti-platelet effects of omega-3 derived metabolites. University of Manitoba, Canada Background: Arachidonic acid ARA derived eicosanoids influence renal hemodynamics, inflammation, and injury.

Methods: To investigate the effects of ALA on early obesity-related glomerulopathy and the renal eicosanoid lipidome, diet-induced obese rats with similar levels of obesity were provided with seven diets containing a wide range of ALA levels and n6:n3 ratios.

Prostanoids have been associated with later stages of renal disease and glomerulomegaly. Soy , renal HOTrE levels were 3-fold greater.

Conclusions: Novel renal eicosanoids produced in vivo with ALA enriched diets were identified. Delivery gestational age was based on ultrasound in the second trimester of pregnancy.

Weight, length and head circumference were obtained at birth. Results: Women in both groups consumed similar numbers of capsules mean 2.

DHA increased mean gestational age from Conclusion: DHA supplementation at this level is safe, Prenatal supplementation increased gestation duration, DHA status markers in mother and newborn, birth weight, length, and head circumference.

Supported by 1R01 HD The effects of ruminant trans fatty acids R-TFA have only been studied recently. Similarly, other epidemiological studies also indicated the lack of association between R-TFA intake and cardiovascular risk.

Intervention studies carried out in Canada and France were published at the beginning of the present Century.

These data suggested that, at least at usual levels of consumption, there is no association between R-TFA intake and cholesterol-dependant cardiovascular risk factors, but men and women appeared to present different patterns.

To draw definitive conclusion, we conducted a meta-analysis including all the intervention studies in healthy volunteers with at least one experimental group with documented R-TFA intake.

From thirteen studies that met all our selection criteria, we extracted data from one or several groups, yielding to twenty-two observations.

Daily intakes of R-TFA ranged from 0. However, further analysis such as multivariate analysis including confounders would be relevant to confirm these results.

Trepanier, A. Domenichiello, Z. Liu, R. Bazinet University of Toronto, Canada Background: Eicosapentaenoic acid EPA is currently under investigation as a potential treatment for neurological disorders such as bipolar disorder and major depression; even though, in the brain, its function is poorly understood and the levels of EPA are fold lower than docosahexaenoic acid DHA.

Freeliving rats were infused at steady state for 5 minutes via the tail vein and blood samples were collected throughout infusion via jugular vein catheter.

After 5 minutes, rats were subjected to high-energy, headfocused microwave irradiation and brains were collected.

Preliminary results: Radioactivity in the aqueous fraction decreased significantly in MEP-treated brain compared to vehicle controls palmitate: 3.

This was accompanied by a significant increase in total lipid radioactivity of MEP-treated brains as compared to controls palmitate: 1.

Future analysis: Radioactivity in various neutral lipids and phospholipid fractions will be analyzed and the identities of radiolabeled fatty acids will be determined.

Thomas, Iris J. Edwards, Isabelle M. Berquin Departments of Cancer Biology, Biochemistry, Pathology; Wake Forest School of Medicine, USA Phospholipids are crucial components of cellular membranes as well as signaling molecules, with fatty acids at the sn-1 and sn-2 position of the glycerol backbone, and choline, ethanolamine, serine or inositol at the sn-3 position.

AKT is a serine-threonine protein kinase that plays important roles in cell growth, proliferation and apoptosis.

It is well documented that AKT activation requires its binding to phosphatidylinositol phosphates PIPs with phosphate groups at positions 3, 4 [i.

PI 3,4 P2] and 3,4,5 [i. PI 3,4,5 P3] on the inositol ring. However, it is unclear whether fatty acids at the sn-1 and sn-2 position can affect the ability of PIPs to activate AKT.

Here we show that dietary polyunsaturated fatty acids PUFA modify phospholipid structure.

Our study suggests that dietary fat, through the structural modification of phospholipids, can affect the AKT signaling pathway that is critical in the development of human cancers.

However, the mechanism is not clear. We also studied the correlation between NF-KB signaling and tumor weight in rat mammary tumor.

Western blot analysis was performed on whole cells, cytosol and nuclear fractions for the NF-KB signaling protein expression.

Methods: Forty healthy participants were recruited. Pre-supplementation control : A single oral dose of 50 mg of 13C-DHA was given to the participants at breakfast, and its appearance in plasma and betaoxidation was monitored for 28 days.

A supplement 3. Post-supplement: In the last 28 days of the supplementation, a single oral dose of 50 mg of 13C-DHA was given to the participants to follow its metabolism.

Post-supplement, cumulative beta-oxidation was 1. Carlson, Carol L. Cheatham, D. Jill Shaddy, Kathleen M. Gustafson, Kathleen N.

Kannass, Caitlin C. Docosahexaenoic acid DHA , which is found in high concentration in the brain, is specifically thought to affect cognitive function.

At delivery infants were randomly assigned to formulas varying in DHA content: 0. Arachidonic acid was present at 0. Formulas were fed to 12 mo of age.

Results: Seventy of 86 infants followed over the long-term remained in the study through 60 mos.

Analyses included Formula and for repeated tests Age. Further support comes from significant progress in understanding the neurophysiology of DHA at the cellular and lipidomic levels, and in animal models of neurodegenerative disease.

Hence, there is considerable momentum reinforcing the concept of a protective effect of DHA on cognition in the elderly. Hence, there is a problem in the human studies on AD, i.

The focus of this talk will therefore be on discussing two themes that may bridge this disconnect: i human studies of DHA levels in AD brain and plasma, and ii changing DHA homeostasis in the elderly.

The emerging recognition that two important risk factors for AD, i. This abnormality is thought to be a factor for the increased tendency of blood cells of SCD patients to aggregate and adhere to vascular endothelium and subsequently precipitate vas-occlusive crisis and organ damage.

However, sickle cell patients are under oxidative stress and this could be aggravated by supplementation. Plasma alpha-tocopherol vit E , and red blood cell antioxidant enzymes and dimethy acetals marker of plasmalogen status were analysed at baseline and six-month supplementation.

Vit E was assessed in a sub-group of patients after one year. The activities of Se-GPx There was no difference in percent total dimethylacetals in CPG 0.

Plasma vit E concentration increased after one year supplementation Hence, it should be safe to supplement sickle cell patients to help ameliorate membrane abnormality and vaso-occlusive crisis.

We wanted to assess whether supplementation of omega-3 LCPUFAs increases the omega-3 LCPUFA concentration in serum, skeletal muscle and adipose tissue, improves vascular function and morphology and lowers inflammation in obese adolescents.

We also wanted to investigate effects on glucose and insulin homeostasis. Methods: 25 obese adolescents 14 females, 11 males, age The study was performed in a double blind, crossover design with 6 weeks washout period.

Anthropometry, blood pressure measurements and fasting blood samples were obtained before and after each treatment period.

Vascular structure and function were measured, intravenous glucose tolerance test IVGTT and euglycemic-hyperinsulinemic clamp were performed, and adipose tissue and skeletal muscle biopsies were obtained after each treatment period.

No difference in total cholesterol, triacylglycerol, HDL cholesterol, anthropometry, blood pressure, pulse wave velocity or vascular structure could be found.

In males, none of these parameters was influenced by omega-3 supplementation. Daily supplementation with omega-3 LCPUFA capsules to obese adolescents increases serum, skeletal muscle and adipose tissue omega-3 LCPUFA concentration, improves vascular function and lowers the degree of inflammation.

It also improves glucose and insulin homeostasis in obese girls without influencing body weight. Since the identities of leaness-promoting bacteria are unknown, we tested an alternative strategy: genetically engineering gut bacteria to secrete mediators known to reduce fat intake.

N-acyl-phosphatidylethanolamines NAPEs are normally synthesized in the small intestine and their metabolites, N-acyl ethanolamides NAEs , increase satiety and decrease food intake.

We transformed the probiotic E. Four groups of C57BL6 mice 10 mice each received one of four treatments in their drinking water: no additive untreated , 0.

All groups were also fed a high-fat diet ad libitum for 8 weeks. Koalin consumption, a measure of gastric distress in mice, was similar in all four groups.

We then stopped treatment of drinking water while continuing high-fat feeding for 4 additional weeks. Post-treatment body weight gain for mice previously administered pAT-EcN was 1.

These findings suggest that consumption of probiotics engineered to express NAPE may be a useful treatment strategy for obesity. Dietary n-3 polyunsaturated fatty acid regulation of adipokines and inflammatory mediators in adipocyte-macrophage paracrine interactions in vitro De Boer, Anna A; Robinson L.

University of Guelph, Canada In obesity, paracrine interactions between adipocytes and infiltrating macrophages in adipose tissue generate inflammation and related complications.

Similar results were found in the trans-well system, although in all fatty acid groups, adipokine secretion was nearly two-fold lower from the trans-well co-culture, emphasizing the importance of direct adipocyte-macrophage contact in paracrine interactions.

The trans-well co-culture system allowed for isolation of adipocytes to measure mRNA expression of pro-inflammatory mediators.

Overall, these data demonstrate that long-chain n-3 PUFA can decrease pro-inflammatory adipokine secretion and mRNA expression of various pro-inflammatory mediators and thus may provide a beneficial strategy to reduce inflammation in an obese state characterized by macrophage infiltration into adipose tissue.

Ouwehand, J. Research Institute, Faculty of Psychology and Education, VU University Amsterdam, Netherlands; Department of Psychiatry and Neuropsychology, Maastricht University, Netherlands Fish consumption has shown its benefits for cognitive functioning in the elderly or children with disorders e.

Therefore an observational study in Dutch high school students aged years was executed. Fish consumption data, end term grades, scores on the Amsterdam Vocabulary Test, and scores on the Youth Self-Report were collected.

Results revealed that Thus, our findings suggest that irrespective of sex, age, and educational track, the association between fish consumption and cognitive performance and academic achievement in adolescents consists of an inverted U-shape.

Higher fish intake was associated with more advanced vocabulary and higher end term grades. However, eating more fish than the described recommended amount seemed no longer beneficial.

The differences found between the groups e. The difference in z-score between the mg fish group and the highest fish consumption group equals 0.

This difference in fish consumption could therefore account for the difference between passing or failing. Procedure: Two groups of dams were fed during gestation and lactation with either a deficient ALA-palm diet containing minimal ALA level 0.

The present study demonstrates that ALA is a very potent inhibitor of the apoptosis induced by the tumor necrosis factor TNF in cardiomyocytes.

Indeed, after short exposure to TNF, survival cascades are promoted in cardiac cells, while a long-lasting cytokine stimulus causes apoptosis.

ALA pre-treatment inhibits the onset of the apoptosis in cardiomyocytes through a mechanism involving caveolae. In fact, in the presence of ALA, caveolin-3 expression is enhanced and the internalization of the TNF receptor, located into the caveolae, is inhibited determining the abortion of the apoptotic vs.

Hagel, D. Werner, B. Chiapinelli, N. Afshordel, S. Eckert, D. The composition of the lipid matrix is, perhaps, the most important allosteric modulator of GPCR function.

I will also address opportunities to study receptor structure in the lipid matrix at close to functional conditions by solid state NMR.

Cardiac Metabolism, University of Maastricht, Netherlands Transport of fatty acids is regulated by membrane fatty acid transporters, e.

In recent years common genetic variants of these proteins have been identified and were found to associate with circulating lipid profiles and metabolic phenotypes.

For instance, subjects with CD36 gene variants that result in a lower CD36 expression level were found to be less susceptible to the metabolic complications of obesity.

Likewise, common variants of the liver-type FABP were reported to influence insulin resistance and type 2 diabetes.

In view of the still emerging functions of these fatty acid-binding proteins, such as the role of CD36 in fat taste perception and that of CD36 and cytoplasmic FABPs in lipid signal transduction and inflammation, common gene variants are expected to contribute to individual variability in these parameters.

These new developments as well as our current understanding of the underlying molecular mechanisms will be discussed in this lecture.

Division of Metabolism, Endocrinology and Nutrition, Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, WA The accumulation of cholesterol by artery wall macrophages plays a critical role in atherosclerosis, the leading cause of cardiovascular disease.

HDL has been proposed to become dysfunctional in subjects with atherosclerosis, but the underlying mechanisms are poorly understood.

One potential pathway involves myeloperoxidase MPO , a potent source of reactive intermediates in human artery wall macrophages.

We used mass spectrometry to demonstrate that apoA-I of HDL isolated from patients established heart disease exhibits site-specific chlorination of tyrosine, a characteristic product of MPO.

University of British Columbia, Canada During stroke, neurons that are deprived of their normal substrates can show signs of structural damage to dendrites after as little as 2 min of ischemia.

Mitochondria also become depolarized within minutes after ishcemia. Mitochondrial dysfunction and the opening of the mitochondrial permeability transition pore mPTP are proposed to link ischemic ionic imbalance to mitochondrially mediated cell death pathways.

Some neurons escape damage within the penumbra. Over time weeks , surviving brain tissue is thought to compensate for regions lost to stroke.

It is generally assumed that recovery is a process that occurs over weeks and involves both the formation of new structural circuits and the alternative use of spared circuits.

Recovery after a small stroke may involve spared peri-infarct tissue with function similar to the infarct.

In contrast, after a large stroke, tissue with similar function may only be found at more distant sites or regions within the unaffected contralateral hemisphere where structural remodeling can be observed.

Using a large bilateral craniotomy preparation in mouse, we show that targeted ischemia to even a single arteriole causes alterations in the patterns of sensory-evoked activity that extend beyond peri-infarct areas into somatotopic regions of the unaffected hemisphere as early as 30 min after stroke onset.

These findings suggest that existing sensory pathways are capable of redistributing activity to even the contralateral hemisphere. To assess changes in functional connectivity after stroke, we are developing an automated approach to monitor intrahemispheric and interhemispheric functional relationships by the activation of Channelrhodopsin-2 ChR2 -expressing cortical neurons at arbitrary cortical points in transgenic mice.

To monitor regional cortical activity we employ organic voltage sensitive dyes. We extend the point stimulation to areas targeting association cortices and secondary somatosensory regions that are inaccessible to direct stimulation via the senses and could potentially contribute to reorganized circuitry.

We apply graph theory and complex network analysis to connection matrices derived from these functional maps to elucidate reciprocal connections between primary and secondary sensory areas, identify network hubs, and determine asymmetries in intracortical connectivity.

We anticipate that new approaches to both monitor and manipulate neuronal function will be important to describe how spared cortical circuits compensate for brain tissue lost to stroke.

M; Maggie Strable Departments of Biochemistry and of Nutritional Sciences, University of Wisconsin-Madison, Madison Wisconsin, USA Dietary fatty acids or fatty acids synthesized de novo in conjunction with nuclear receptors and transcription factors affect the transcription of a variety of genes.

The mechanisms by which these interactions and consequent effects of the individual class of fatty acids occur is proving to be complicated and yet it is invaluable to our understanding of the role that dietary fat can play in disease management and prevention.

We have used the stearoyl-CoA desaturase SCD mouse model to investigate the role of de novo synthesized fatty acids in the regulation of lipogenic gene expression.

Past work demonstrated that SCD1 deficiency impairs hepatic lipogenesis and protects against diet-induced obesity.

To address this, we produced liver-specific transgenic mice expressing human SCD5, which preferentially synthesizes oleate n-9 , and introduced this transgene into GKO mice.

Hepatic oleate synthesis increased plasma glucose levels and largely prevented very-low-fat diet-induced weight loss.

This work suggests that hepatic MUFA are involved in regulation of lipogenesis and gluconeogenesis. Supported by NIH.

Within a single generation populations that once were the focus of remedial supplementation programmes aimed at preventing malnutrition are now the focus of anti-obesity campaigns.

Many countries have passed through the 'nutrition transition' and others are rapidly progressing. The desirability, affordability and abundance of refined vegetable oils has resulted in major changes in fat intake as a proportion of energy.

The quality and type of oils is highly variable and may be having profound health effects that have yet to be properly explored.

Despite this progress in many nations there remain large swathes of poverty where fat intakes may be marginal; creating a low-energy density in diets that compromises children's ability to ingest sufficient energy and potentially impairing the absorption of fat-soluble vitamins.

Essential fatty acid intakes are frequently compromised in pregnancy and young childhood, though there is great heterogeneity among studies.

Some of this heterogeneity may be caused by methodological issues, particularly in respect of accurately assaying the minor components of fatty acid profiles such as the long-chain PUFAs, and international ecological studies using standardised methodologies would be highly desirable.

Lipid-based nutrient supplements LNS provide a particularly suitable vehicle for enhancing the essential fatty acid itakes of the most at-risk mothers and children and the many on-going research challenges will be summarised.

The Role of Highly Unsaturated Fatty Acids in the Health and Disease of the Retina SanGiovanni, John Paul NEI,National Institutes of Health, USA The presentation will include: 1 an overview of extant work characterizing the capacity of diet-based fatty acids, their precursors, and metabolites to alter retinal structure and function; 2 discussion of a genomic systems-based approach to investigate relationship of receptors, transporters, enzymes and hormones impacting or impacted by these molecules in the context of pathogenesis of eye diseases manifesting neovascular and neurodegenerative components; and, 3 commentary on promising venues for development of preventive and therapeutic applications identified via the systems-based approach.

New endogenous mechanisms involved in the resolution of acute self-limited inflammatory exudates have provided insight into the control of both host defense and local acute inflammation.

Using a systems approach coupled with lipid mediator LM -metabololipidomics that we introduced, permitted the identification of several new families of potent local acting bioactive lipid-derived mediators in resolving exudates CN Serhan et al Nature Immunology This presentation shall update new advances on the biosynthesis and functions of the founding members of this novel genus of specialized pro-resolving mediators SPM and their roles as agonists of resolution.

The SPM include 3 families of chemical mediators: resolvins, protectins and the most recent addition, maresins from macrophages.

These are local autacoids biosynthesized in resolving exudates from essential omega-3 fatty acids n-3, EPA and DHA that possess potent multi-pronged anti-inflammatory, pro-resolving, reduce pain and microbial clearance actions in animal models.

Low dose aspirin also triggers production of endogenous chiral epimers from certain of SPM pathways that have to be proven bioactive and stimulate resolution.

Many other research groups worldwide now confirm endogenous formation of resolvins and protectins and their organ-protective roles and the first Rv is currently in human clinical trial.

For example, SPM have potent actions in murine ischemic renal injury, obesity-induced insulin resistance and liver disease, murine colitis and arthritis, as well as reducing pain.

These findings change the old concept that resolution of inflammation is a passive process. Together, they indicate that natural resolution pathways may underlie many prevalent diseases associated with uncontrolled inflammation and open the potential for resolutionbased therapeutics.

Triglyceride Digestion and Transport Tso, Patrick The focus of my talk will be on the digestion and absorption of dietary biliary lipids in the gastrointestinal tract, and the physiology of this event.

The digestion of dietary triacylglycerol TG begins in the stomach and continues in the intestinal lumen. Both gastric lipase and pancreatic lipase contribute to its digestion.

Following this initial breakdown of dietary TG, the hydrolytic products, monoacylglycerols MG and fatty acids FA , are solubilized in micelles and taken into the enterocyte by both passive as well as carrier mediated processes.

The importance of the unstirred water layer to the uptake of TG digestion products, as proposed by Dr. John Dietschy, will be described.

I will also focus on the uptake of cholesterol by the enterocytes, via the NPC1L1 transporter. Following uptake into the enterocute, MG and FA are transported from the apical membrane to the endoplasmic reticulum, and re-esterified to form TG involving various enzymes.

I will also focus on the mechanism of chylomicron formation in the enterocytes, and the role of the microsomal triglyceride transfer protein in regulating the process of chylomicron formation.

Additionally, the trafficking of chylomicron particles from the endoplasmic reticulum to the Golgi apparatus will be described, as well as the process of chylomicron exocytosis and how they journey to the lacteals.

I plan to conclude the talk with a discussion of the role of various apolipoproteins in intestinal lipid transport by the enterocytes and how the conscious lymph fistula mouse model has contributed to our knowledge of the subject.

This lecture will examine the relationship between fatty acid composition and immune function, evaluate the influence of ageing on responsiveness of the immune system to n-3 polyunsaturated fatty acids PUFA , describe the role of lipid rafts in immunomodulation by fatty acids, highlight advances in eicosanoid biology, and describe emerging receptors as targets for action by fatty acids.

Hess, Manabu T. Among the most critical developments in this process is the biogenesis of an organelle unique to sperm, the acrosome, whose construction is dependent on stage-specific vesicular trafficking and membrane fusion events.

Deficiency in docosahexaenoic acid DHA was recently shown to result in a failure of acrosome biogenesis; however a role for DHA in membrane fusion has yet to be defined.

Similarly, we show by immunohistochemistry that the intracellular localization of acrosin a cargo protein of proacrosomal vesicles is normally distributed in early Golgi-phase spermatids, but in subsequent phases of spermiogenesis is dispersed throughout the cytosol in an abnormal punctate pattern.

Further, membrane fusion proteins syntaxin2 and VAMP4 displayed aberrant accumulation throughout spermiogenesis; and endoplasmic reticulum cisternae, as well as smaller transport vesicles, were present in excess on the cis-face of the Golgi, each suggestive of impaired intracellular transport or fusion.

Modulation of normal rat colon mucosa highlighted the differential effects of fish and borage oils on certain lipid and FA parameters.

ACF formation was significantly enhanced by fish oil, whereas borage oil counteracted this effect. However, the efficacy of the intervention appears to be determined by the respective stage in carcinogenesis.

S, and Anderson R. We used a skin-specific promoter to drive the expression of ELOVL4 protein thereby generating animals with global Elolvl4 deletion except in the skin.

The skin rescued mice are runts, have defects in eyelid opening, and die within the first three weeks from birth.

This regulation extends to the sub-cellular compartments that make up the cellular architecture. Moreover, lipids help recruit proteins to specific locations and maintain their function.

Determining spatiality at the subcellular level how the lipid composition varies is therefore very important in terms of understanding the role sub-cellular compartmentation plays in regulating cellular metabolism.

To demonstrate this approach this study reports a comprehensive analysis of the subcellular proteome and lipidome of a hepatoma cell line FaO and its utility for monitoring sub-cellular changes associated with Non-Genotoxic Carcinogens NGCs exemplified by Mono 2-ethylhexyl phthalate MEHP.

A self-generating density gradient was used to partially separate organelles into individual fractions. Fractions were selected based on their profile of proteins, measured by western blotting.

Distributions were then determined by isobaric mass tagging, LC-MS and multivariate data analysis, based on proteins with known organelle locations.

This analysis of enriched organelle fractions identified numerous lipid species, whose type and concentration varied between different organelles.

Following MEHP treatment, changes were seen in the observed distribution and concentration of the lipids including PtdEtn and PtdIns throughout the gradient, supporting the hypothesis that the some of the changes in the lipid profiles, due to NGCs, are a result of induced organelle proliferation.

Here we present a rapid few seconds , real time method to analyze the fatty acid profiles in food and biological samples. To illustrate the potential of this approach we analyzed lipid profiles of edible oils e.

Samples were swiped on a capillary and placed near the mass spectrometer ion source. Lipids were ionizated by DART, separated by ion mobility msec and mass analyzed by the time-of-flight mass analyzer.

This generated 3D maps drift time, exact mass, and intensity of the sample composition at the molecular level.

Our approach of analysis is suitable for the rapid screening of various bioactive lipids, e. Potential applications include fingerprinting of biological phenotypes and comparative lipidomic analysis in the areas of personalized medicine, disease diagnostics and food analysis.

Consumption of a diet high in saturated- and trans- fatty acids increases risk of cardiovascular disease. However, consumption of the dietary trans fatty acids conjugated linoleic acids CLA may protect against cardiovascular disease and improve platelet function.

Many issues relating to the potential mechanism of protection are unknown. Platelet proteins from washed human platelets were separated in a total of protein spots using 2-dimensional gel electrophoresis.

Pathway analysis based on KEGG pathways revealed that the majority of these proteins was involved in regulation of the cytoskeleton and platelet structure, or receptor activity, signalling and focal adhesion.

These proteins, or indeed downstream proteins or metabolites, could be candidate biomarkers to measure the efficacy of fatty acids on platelet function in future nutritional intervention studies.

In the present study we fed Zucker rats with 0. In addition, the decreased ratio was associated to a lower deposition of ectopic fat in liver and heart, plasma NEFA, glycemia and insulin resistance.

We may conclude that endocannabinoid balance between visceral and subcutaneous adipose tissues is crucial for body fat homeostasis and low doses of dietary n-3PC are able to affect significantly this balance and significantly improve metabolic syndrome in obese zucker rats.

University of Western Australia, Australia Background: Overweight people are at risk of developing heart disease due to their predisposition of also having high blood pressure, lipids and glucose levels.

The cytochrome P metabolites of arachidonic acid are important regulators of vascular function and homeostasis.

This study examined metabolism of arachidonic acid by the cytochrome P epoxygenase that leads to formation of 4 epoxyeicosatrienoic acid EET regioisomers.

EETs are vasodilators, and inhibit platelet aggregation. Their actions are attenuated by metabolism to dihydroxyeicosatrianoic acids DHETs by soluble epoxide hydrolase.

Their possible contribution to cardiovascular risk has not been assessed in overweight humans. Results: The volunteers were aged Plasma DHETs were not different between the groups Platelet DHETs were not different between the groups 0.

Conclusions: The increase in plasma EETs in the MetS may be a homeostatic response to elevated blood pressure or increased circulating vasoconstrictors that have been linked to insulin resistance in these subjects.

The reduced platelet EETs levels may be of relevance to increased platelet reactivity and aspirin resistance that has been described in subjects with the metabolic syndrome.

Litmanovitz, K. Davidson, A. Eliakim, R. Regev, T. Dolfin, Y. Lifshitz, D. Contrary, palmitic-acid in the sn-1 and sn-3 positions, the predominantly fat composition in regular infant formulas, is hydrolyzed by pancreatic lipase, resulting in free palmitic-acid that forms poorly absorbed complexes with calcium, also associated with lower bones calcium deposition and abdominal discomfort.

Anthropometrics and bone SOS by quantitative ultrasound Sunlight Omnisense were measured at randomization, and at 6 and 12 weeks postnatal.

Before each visit parents filled a three days report on infant feeding, stool characteristics and crying. Results: There were no significant differences in anthropometrics at randomization and at 12 weeks postnatal.

Infants in the InFat group had less episodes of crying per day and significant decrease in daily crying compared to Control group.

Conclusion: The consumption of InFat formula by term infants for 12 weeks had beneficial effects on bone SOS compared to regular Control formula and was most similar to the breastfed group.

Pipingas, A. Z Ament, Z. Swinburne University of Technology, Melbourne, Australia Background: Recent evidence suggests that, although only present in low quantities in the brain, eicosapentaenoic acids omega-3 fatty acid EPA , enhances early visual cortical processing measured with multifocal visual evoked potentials Bauer et al.

However, while docosahexaenoic omega-3 fatty acid DHA has been shown to increase neural activity during a sustained visual attention task McNamara et al.

Supplementations were administered using a double-blind, crossover design, with a day washout period between the two supplementation periods.

Participants were scanned at Baseline prior to supplementation , and after each day supplementation period. Reaction times and response accuracy were recorded.

Results: The EPA-rich supplementation was associated with a reduction in functional activation in the anterior cingulate cortex ACC when compared to Baseline.

Conclusions: Reduced brain functional activation, coupled with faster reaction times during a Stroop Color Word Interference Task suggests a mechanism of improved neural efficiency following a day EPA-rich supplementation.

Effects of iron and n-3 fatty acid supplementation, alone and in combination, on cognition: a randomized, double-blind, placebo controlled intervention in iron-deficient South African school children Baumgartner, Jeannine; CM Smuts, L Malan, MB Zimmermann Centre of Excellence in Nutrition, North-West University, Potchefstroom, South Africa; Laboratory of Human Nutrition, Institute of Food, Nutrition and Health, Switzerland Background: Little is known about the combined effects of iron and n-3 fatty acid n-3 FA supplementation in children suffering from both deficiencies.

Objective: We investigated whether providing iron and a mixture of docosahexaenoic DHA and eicosapentaenoic acid EPA , alone and in combination, to children with iron deficiency and poor n-3 FA intakes will improve cognitive performance.

No effects on cognition were found in the non-anaemic children. Conclusions: Our findings suggest that iron supplementation may improve verbal and non-verbal learning and memory in children suffering from anaemia.

Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, School of Medicine, USA The significance of the selective enrichment in omega-3 essential fatty acids in the nervous system has remained, until recently, incompletely understood.

We found that NPD1 is promptly made in response to oxidative stress and brain ischemia-reperfusion, and in the presence of neurotrophins.

We will present the following studies: 1 DHA i. Neurological function was evaluated on up to 7 days after MCAo.

DHA improved behavioral scores and reduced cortical , subcortical and total infarct volumes 7 days after stroke. In addition, DHA reduced microglia infiltration and increased number of astrocytes and neurons.

Then we performed the total chemical synthesis of this molecule and tested the novel AT-NPD1 by iv 1 hr after 2h middle cerebral artery occlusion in rats.

Brain edema, computed from T2WI in the cortex penumbra and striatum core , was elevated in the saline group. In conclusion NPD1 targets neuroinflammatory signaling at various check points as well as modulates apoptotic cascades and other forms of cell death in turn promoting homeostatic regulation of neuronal circuitry integrity in experimental stroke.

In this talk, I will review how polyunsaturated fatty acids PUFA enter the brain, and the mechanisms that regulate their concentrations within brain phospholipids.

Whereas little evidence exists to support the incorporation of PUFA from lipoproteins into the brain, the incorporation rates of arachidonic and docosahexaenoic acid from the plasma unesterified pool into brain phospholipids closely approximate independent measures of their consumption rates by the brain.

Thus, with the use of radiolabelled fatty acids, it is possible to image and quantify their entry and uptake into the brain in rodents and, with positron emission tomography, in humans.

Upon entry into the brain, certain PUFA are highly conserved with extensive recycling within phospholipids, whereas others, such as eicosapentaenoic acid, are rapidly and extensively removed from the brain, in part, due to b-oxidation.

Identifying the mechanisms by which PUFA enter and are handled within the brain could lead to a better understanding of nutritional requirements for the brain as well as new therapeutic targets and novel imaging methods.

Background: Membrane phospholipid metabolism and redox regulation may be disturbed in schizophrenia. This has entailed randomised controlled trials with either omega-3 fatty acids or redox regulators.

The present study examines the effects of combining these agents. We hypothesized that lower baseline levels of polyunsaturated fatty acids PUFA would predict more benefit from trial drugs.

Patients aged years with DSM-IV schizophrenia, schizoaffective or schizophreniform disorders were consecutively included at admission to hospital.

Results: Ninety-nine patients were included. At baseline, erythrocyte PUFA were measured in 97 subjects. PUFA were bimodally distributed low, high.

Trial drugs had clinical effects beyond psychotic symptoms, mainly in low PUFA patients. When these agents are combined, they seem safe.

Diets rich in long-chain w-3 polyunsaturated fatty acids, namely docosahexaenoic acid DHA and eicosapentaenoic acid EPA , have been shown to have many beneficial effects such as the improvement of insulin sensitivity with beneficial effects against obesity and the prevention of cardiovascular diseases.

The content and the expression of adiponectin in adipose tissues were also measured 2 to evaluate the effects of DHA and EPA and their respective oxygenated metabolites on adiponectin secretion by 3T3-L1 adipocytes.

In all three white adipose tissues subcutaneous, epididymal and retroperitoneal tissues , the adipokine content was not significantly different between mice fed the w-3 polyunsaturated fatty acid-rich diet and mice fed with the standard diet.

However, the adiponectin content was dependent on adipose tissue depot. Adiponectin gene expression was significantly increased in epididymal and subcutaneous tissues of DHA-fed mice compared to control mice.

Our studies show that DHA and EPA rapidly improved the profile of secreted adiponectin in mice and in 3T3-L1 adipocytes and suggest that this effect may be mediated by their respective oxygenated metabolites.

These data confirm that dietary intake of w-3 polyunsaturated fatty acids may be beneficial for prevention or treatment of cardiovascular and obesity-associated diseases.

Myristoylated and palmitoylated proteins in the regulation of apoptosis and metabolism revealed through proteomic Berthiaume, Luc G; Dale D.

Martin, Morris A. Kostiuk, Megan C. Yap and Erwan Beauchamp Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Canada Fatty acylation, the attachment of fatty acids to proteins, is a critical mechanism of cellular control.

It impacts virtually every aspect of cellular life. Using chemical biology, we and others recently developed approaches leading to the rapid detection, identification and characterization of acylated proteins using azido- and alkynyl fatty acid analogs.

Myristoylation is the co- or post-translational attachment of myristate to N-terminal glycine residues of proteins.

Very little is known about post-translational myristoylation and our new characterization efforts resulted in the demonstration that 15 or more post-translationally myristoylated proteins exist in various cell lines undergoing apoptosis and in the identification of 5 of these with life and death implications for the cell.

Palmitoylation, the modification of proteins by palmitate, is known as a key membrane tethering and cellular localization mechanism.

In addition, we recently identified 21 palmitoylated proteins in mitochondria, where palmitoylation had various and profound effects on the catalytic activity and function of the modified proteins, with new implications in the regulation of metabolism.

In summary, we will present several examples illustrating how chemical biology approaches using click chemistry can catalyze the discovery of new roles for fatty acids in the regulation of cell death mechanisms and metabolism.

Objective: To investigate the association between levels of polyunsaturated fatty acids PUFA in maternal whole blood at week 24 of gestation and multiple lifestyle factors.

Data on socioeconomic and lifestyle factors was obtained prospectively during visits to the research unit, and fatty acid compositions of whole blood were determined.

Covariates that were significantly associated with the dependent variable in the univariate analyses were included in a stepwise backwards elimination multivariate model with a cut-off P-value of 0.

Results: We found independent positive significant associations between all n-3 PUFA variables and high education, high income, non-smoking, and being primiparious.

The n-6 PUFA variables were not associated with any of the factors. None of the preselected PUFA variables were associated with maternal age and asthma, urban living, or gender of the child.

Thus, when analyzing associations between n-3 PUFAstatus and health, the socioeconomic and lifestyle factors that have an independent association with both blood fatty acid composition and health must be taken into consideration.

Whale blubber was part of the traditional Eskimo diet. After news ads and telephone screening, participants were assessed for inclusion by a doctor.

Marine omega-3 fatty acid intake was restricted in a two week run-in period and during the 6 week intervention period.

Urinary F2 isoprostanes were generally low though significantly increased in WO group after 6 weeks, but not compared with FO group.

In conclusion; whale oil may possibly be as good an omega-3 source as fish oil, when given in equivalent medium dosage in the present short-term bioavailability study in healthy volunteers with a relatively high baseline omega-3 intake.

Information on source is uniquely retained by intrinsic stable isotope ratios, while kinetics and pool characteristics can be obtained starting with a specific enriched compound and following the transfer of label to products.

Most food plants operate with the C3 pathway, with corn using the C4 pathway. The acetate pool in animal cells has input from all sources of dietary carbon and thus reflects the mix of C3 and C4 plants in the diet.

Three examples will be presented. Carbon isotope analysis reveals that the major retinal saturated and monounsaturated fatty acids originate with corn, while DHA and n-3 both originate with C3 plants that were likely to be incidental feed components.

Steroid hormones and their metabolites reflect the dietary mix of C3 and C4 plants, with input from preformed dietary cholesterol.

These techniques were instrumental in establishing the biosynthetic efficiency for the conversion of precursor PUFA linoleic and linolenic acids to highly unsaturated fatty acids in pregnant and neonate non-human primates and humans.

Diets of the treatment groups were supplemented with chia or flax after 8 wk on H diet for a further 8 wk.

Compared to the H rats, ALA-supplemented rats had improved insulin sensitivity and glucose tolerance, reduced visceral adiposity, decreased hepatic steatosis, reduced cardiac and hepatic inflammation and fibrosis without changes in plasma lipids or blood pressure.

Stearoyl-CoA desaturase-1 inhibition was shown as an increase in the substrate concentrations together with depletion of products in the heart, liver and the adipose tissue of ALA-supplemented rats.

The Ctrans-7 was preferentially stored in the adipose tissue; the relatively inert Cn-9 was stored in sensitive organs such as liver and heart and Cn-6, the parent fatty acid of the n-6 pathway, was preferentially metabolised.

Thus, ALA induces lipid redistribution associated with cardioprotection and hepatoprotection following reduced inflammatory cell infiltration.

These results strongly suggest that ALA produces pharmacological responses independent of conversion to longer chain fatty acids in inflammatory conditions such as metabolic syndrome and arthritis.

Design and methods: In an open-label randomized, controlled trial, healthy pregnant women either received a dietary intervention [supplementation with mg n-3 LCPUFAs per day and a dietary counseling to reduce AA intake] from 15th week of gestation until 4 months of lactation or followed their habitual diet.

Breastmilk fatty acid profile was analysed at 6 weeks and 4 months postpartum. Multiple regression models adjusting for relevant confounders were performed to determine the relationship between breastmilk fatty acid composition and infant fat mass assessed by skinfold thickness measurements and abdominal sonography up to 1 year pp.

AA content was comparable between both groups. Conclusion: Breastmilk n-3 fatty acids appear to stimulate fat mass growth over the 1st year of life whereas AA seems to be involved in the regulation of overall growth especially in the early postpartum period.

Individuals with type 2 diabetes are at high risk for cardiovascular events. Eicosapentaenoic acid EPA -derived resolvin lipid mediators have been shown to decrease platelet activation in ex-vivo human samples.

Platelet spreading, platelet granulate content release, and platelet receptor conformational changes are all correlated with increased cardiovascular disease.

When compared to untreated controls, there was a significant decrease in the percentage of spread platelets after treatment with increasing concentrations of 17R-resolvin D1, untreated A significant decrease in spreading was also observed when both 17 R and 17S-resolvin D1 were used in combination, untreated Our results suggest that DHA-derived resolvin lipid mediators have modest anti-platelet effects as quantified by platelet cell surface markers of activation and morphological spreading evaluation in individuals with and without type 2 diabetes.

More studies should be conducted to elucidate additional anti-platelet effects of omega-3 derived metabolites. University of Manitoba, Canada Background: Arachidonic acid ARA derived eicosanoids influence renal hemodynamics, inflammation, and injury.

Methods: To investigate the effects of ALA on early obesity-related glomerulopathy and the renal eicosanoid lipidome, diet-induced obese rats with similar levels of obesity were provided with seven diets containing a wide range of ALA levels and n6:n3 ratios.

Prostanoids have been associated with later stages of renal disease and glomerulomegaly. Soy , renal HOTrE levels were 3-fold greater.

Conclusions: Novel renal eicosanoids produced in vivo with ALA enriched diets were identified. Delivery gestational age was based on ultrasound in the second trimester of pregnancy.

Weight, length and head circumference were obtained at birth. Results: Women in both groups consumed similar numbers of capsules mean 2.

DHA increased mean gestational age from Conclusion: DHA supplementation at this level is safe, Prenatal supplementation increased gestation duration, DHA status markers in mother and newborn, birth weight, length, and head circumference.

Supported by 1R01 HD The effects of ruminant trans fatty acids R-TFA have only been studied recently. Similarly, other epidemiological studies also indicated the lack of association between R-TFA intake and cardiovascular risk.

Intervention studies carried out in Canada and France were published at the beginning of the present Century.

These data suggested that, at least at usual levels of consumption, there is no association between R-TFA intake and cholesterol-dependant cardiovascular risk factors, but men and women appeared to present different patterns.

To draw definitive conclusion, we conducted a meta-analysis including all the intervention studies in healthy volunteers with at least one experimental group with documented R-TFA intake.

From thirteen studies that met all our selection criteria, we extracted data from one or several groups, yielding to twenty-two observations.

Daily intakes of R-TFA ranged from 0. However, further analysis such as multivariate analysis including confounders would be relevant to confirm these results.

Trepanier, A. Domenichiello, Z. Liu, R. Bazinet University of Toronto, Canada Background: Eicosapentaenoic acid EPA is currently under investigation as a potential treatment for neurological disorders such as bipolar disorder and major depression; even though, in the brain, its function is poorly understood and the levels of EPA are fold lower than docosahexaenoic acid DHA.

Freeliving rats were infused at steady state for 5 minutes via the tail vein and blood samples were collected throughout infusion via jugular vein catheter.

After 5 minutes, rats were subjected to high-energy, headfocused microwave irradiation and brains were collected.

Preliminary results: Radioactivity in the aqueous fraction decreased significantly in MEP-treated brain compared to vehicle controls palmitate: 3.

This was accompanied by a significant increase in total lipid radioactivity of MEP-treated brains as compared to controls palmitate: 1.

Future analysis: Radioactivity in various neutral lipids and phospholipid fractions will be analyzed and the identities of radiolabeled fatty acids will be determined.

Thomas, Iris J. Edwards, Isabelle M. Berquin Departments of Cancer Biology, Biochemistry, Pathology; Wake Forest School of Medicine, USA Phospholipids are crucial components of cellular membranes as well as signaling molecules, with fatty acids at the sn-1 and sn-2 position of the glycerol backbone, and choline, ethanolamine, serine or inositol at the sn-3 position.

AKT is a serine-threonine protein kinase that plays important roles in cell growth, proliferation and apoptosis.

It is well documented that AKT activation requires its binding to phosphatidylinositol phosphates PIPs with phosphate groups at positions 3, 4 [i.

PI 3,4 P2] and 3,4,5 [i. PI 3,4,5 P3] on the inositol ring. However, it is unclear whether fatty acids at the sn-1 and sn-2 position can affect the ability of PIPs to activate AKT.

Here we show that dietary polyunsaturated fatty acids PUFA modify phospholipid structure. Our study suggests that dietary fat, through the structural modification of phospholipids, can affect the AKT signaling pathway that is critical in the development of human cancers.

However, the mechanism is not clear. We also studied the correlation between NF-KB signaling and tumor weight in rat mammary tumor. Western blot analysis was performed on whole cells, cytosol and nuclear fractions for the NF-KB signaling protein expression.

Methods: Forty healthy participants were recruited. Pre-supplementation control : A single oral dose of 50 mg of 13C-DHA was given to the participants at breakfast, and its appearance in plasma and betaoxidation was monitored for 28 days.

A supplement 3. Post-supplement: In the last 28 days of the supplementation, a single oral dose of 50 mg of 13C-DHA was given to the participants to follow its metabolism.

Post-supplement, cumulative beta-oxidation was 1. Carlson, Carol L. Cheatham, D. Jill Shaddy, Kathleen M.

Gustafson, Kathleen N. Kannass, Caitlin C. Docosahexaenoic acid DHA , which is found in high concentration in the brain, is specifically thought to affect cognitive function.

At delivery infants were randomly assigned to formulas varying in DHA content: 0. Arachidonic acid was present at 0.

Formulas were fed to 12 mo of age. Results: Seventy of 86 infants followed over the long-term remained in the study through 60 mos.

Analyses included Formula and for repeated tests Age. Further support comes from significant progress in understanding the neurophysiology of DHA at the cellular and lipidomic levels, and in animal models of neurodegenerative disease.

Hence, there is considerable momentum reinforcing the concept of a protective effect of DHA on cognition in the elderly.

Hence, there is a problem in the human studies on AD, i. The focus of this talk will therefore be on discussing two themes that may bridge this disconnect: i human studies of DHA levels in AD brain and plasma, and ii changing DHA homeostasis in the elderly.

The emerging recognition that two important risk factors for AD, i. This abnormality is thought to be a factor for the increased tendency of blood cells of SCD patients to aggregate and adhere to vascular endothelium and subsequently precipitate vas-occlusive crisis and organ damage.

However, sickle cell patients are under oxidative stress and this could be aggravated by supplementation. Plasma alpha-tocopherol vit E , and red blood cell antioxidant enzymes and dimethy acetals marker of plasmalogen status were analysed at baseline and six-month supplementation.

Vit E was assessed in a sub-group of patients after one year. The activities of Se-GPx There was no difference in percent total dimethylacetals in CPG 0.

Plasma vit E concentration increased after one year supplementation Hence, it should be safe to supplement sickle cell patients to help ameliorate membrane abnormality and vaso-occlusive crisis.

We wanted to assess whether supplementation of omega-3 LCPUFAs increases the omega-3 LCPUFA concentration in serum, skeletal muscle and adipose tissue, improves vascular function and morphology and lowers inflammation in obese adolescents.

We also wanted to investigate effects on glucose and insulin homeostasis. Methods: 25 obese adolescents 14 females, 11 males, age The study was performed in a double blind, crossover design with 6 weeks washout period.

Anthropometry, blood pressure measurements and fasting blood samples were obtained before and after each treatment period.

Vascular structure and function were measured, intravenous glucose tolerance test IVGTT and euglycemic-hyperinsulinemic clamp were performed, and adipose tissue and skeletal muscle biopsies were obtained after each treatment period.

No difference in total cholesterol, triacylglycerol, HDL cholesterol, anthropometry, blood pressure, pulse wave velocity or vascular structure could be found.

In males, none of these parameters was influenced by omega-3 supplementation. Daily supplementation with omega-3 LCPUFA capsules to obese adolescents increases serum, skeletal muscle and adipose tissue omega-3 LCPUFA concentration, improves vascular function and lowers the degree of inflammation.

It also improves glucose and insulin homeostasis in obese girls without influencing body weight. Since the identities of leaness-promoting bacteria are unknown, we tested an alternative strategy: genetically engineering gut bacteria to secrete mediators known to reduce fat intake.

N-acyl-phosphatidylethanolamines NAPEs are normally synthesized in the small intestine and their metabolites, N-acyl ethanolamides NAEs , increase satiety and decrease food intake.

We transformed the probiotic E. Four groups of C57BL6 mice 10 mice each received one of four treatments in their drinking water: no additive untreated , 0.

All groups were also fed a high-fat diet ad libitum for 8 weeks. Koalin consumption, a measure of gastric distress in mice, was similar in all four groups.

We then stopped treatment of drinking water while continuing high-fat feeding for 4 additional weeks.

Post-treatment body weight gain for mice previously administered pAT-EcN was 1. These findings suggest that consumption of probiotics engineered to express NAPE may be a useful treatment strategy for obesity.

Dietary n-3 polyunsaturated fatty acid regulation of adipokines and inflammatory mediators in adipocyte-macrophage paracrine interactions in vitro De Boer, Anna A; Robinson L.

University of Guelph, Canada In obesity, paracrine interactions between adipocytes and infiltrating macrophages in adipose tissue generate inflammation and related complications.

Similar results were found in the trans-well system, although in all fatty acid groups, adipokine secretion was nearly two-fold lower from the trans-well co-culture, emphasizing the importance of direct adipocyte-macrophage contact in paracrine interactions.

The trans-well co-culture system allowed for isolation of adipocytes to measure mRNA expression of pro-inflammatory mediators.

Overall, these data demonstrate that long-chain n-3 PUFA can decrease pro-inflammatory adipokine secretion and mRNA expression of various pro-inflammatory mediators and thus may provide a beneficial strategy to reduce inflammation in an obese state characterized by macrophage infiltration into adipose tissue.

Ouwehand, J. Research Institute, Faculty of Psychology and Education, VU University Amsterdam, Netherlands; Department of Psychiatry and Neuropsychology, Maastricht University, Netherlands Fish consumption has shown its benefits for cognitive functioning in the elderly or children with disorders e.

Therefore an observational study in Dutch high school students aged years was executed. Fish consumption data, end term grades, scores on the Amsterdam Vocabulary Test, and scores on the Youth Self-Report were collected.

Results revealed that Thus, our findings suggest that irrespective of sex, age, and educational track, the association between fish consumption and cognitive performance and academic achievement in adolescents consists of an inverted U-shape.

Higher fish intake was associated with more advanced vocabulary and higher end term grades. However, eating more fish than the described recommended amount seemed no longer beneficial.

The differences found between the groups e. The difference in z-score between the mg fish group and the highest fish consumption group equals 0.

This difference in fish consumption could therefore account for the difference between passing or failing. Procedure: Two groups of dams were fed during gestation and lactation with either a deficient ALA-palm diet containing minimal ALA level 0.

The present study demonstrates that ALA is a very potent inhibitor of the apoptosis induced by the tumor necrosis factor TNF in cardiomyocytes.

Indeed, after short exposure to TNF, survival cascades are promoted in cardiac cells, while a long-lasting cytokine stimulus causes apoptosis.

ALA pre-treatment inhibits the onset of the apoptosis in cardiomyocytes through a mechanism involving caveolae. In fact, in the presence of ALA, caveolin-3 expression is enhanced and the internalization of the TNF receptor, located into the caveolae, is inhibited determining the abortion of the apoptotic vs.

Hagel, D. Werner, B. Chiapinelli, N. Afshordel, S. Eckert, D. Juan, N. Bazan Dept. In case of a deficit of antioxidants and antioxidant cellular mechanisms the high turnover of oxygen results in the production of reactive oxygen species and ensuing damage of essential biomolecules.

Those deleterious effects accumulate especially in differentiated tissues like the brain. As a major consequence, perturbations of the energy metabolism including mitochondrial dysfunction culminate in functional deficits.

With the increasing average life span of humans, age-related cognitive disorders such as Alzheimer disease AD are a major health concern in our societies.

Strategies for long-term prevention from mitochondrial dysfunction including sufficient supply of essential nutrients may also delay the onset of age-related neurodegenerative diseases.

Neuroprotective properties of FO were assessed ex vivo after 21 days in dissociated brain cells DBC and isolated mitochondria mito.

DHA levels were significantly lower in brains of aged mice and this deficiency was compensated by FO administration.

Our findings provide new mechanisms underlying the neuroprotective actions of polyunsaturated fatty acids and identified FO as promising neutraceutical to delay age-related cerebral alterations.

Supported by: Arbeitskreis Omega-3 e. Forty children aged y were matched in pairs for age, sex and maternal education and randomly assigned to intervention or control treatment.

One group received daily a margarine enriched with either 1. The study had a parallel design and duration of 3 months.

At baseline and end of intervention, fasting blood samples were drawn and analyzed on fatty acid composition of plasma lipids and red blood cell RBC phospholipids and on concentration of blood lipids.

Baseline blood lipid concentrations were on average 0. Results on blood lipid concentration will be presented and discussed.

LCPUFA are rapidly incorporated into the microdomains of the cell membrane lipid rafts where important death and growth receptors and signals are located.

Studies from our laboratory have demonstrated that the incorporation of the DHA and EPA into lipid rafts is associated with reduced epidermal growth factor receptor and increased CD95 Fas in plasma membrane rafts.

These changes were associated with post membrane changes in the signaling pathways and cell growth and apoptosis, thereby providing possible membrane-mediated mechanisms for the effects of n-3 LCPUFA on the survival of human breast cancer cells.

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However, sickle cell patients are under oxidative stress and this could be aggravated by supplementation.

Plasma alpha-tocopherol vit E , and red blood cell antioxidant enzymes and dimethy acetals marker of plasmalogen status were analysed at baseline and six-month supplementation.

Vit E was assessed in a sub-group of patients after one year. The activities of Se-GPx There was no difference in percent total dimethylacetals in CPG 0.

Plasma vit E concentration increased after one year supplementation Hence, it should be safe to supplement sickle cell patients to help ameliorate membrane abnormality and vaso-occlusive crisis.

We wanted to assess whether supplementation of omega-3 LCPUFAs increases the omega-3 LCPUFA concentration in serum, skeletal muscle and adipose tissue, improves vascular function and morphology and lowers inflammation in obese adolescents.

We also wanted to investigate effects on glucose and insulin homeostasis. Methods: 25 obese adolescents 14 females, 11 males, age The study was performed in a double blind, crossover design with 6 weeks washout period.

Anthropometry, blood pressure measurements and fasting blood samples were obtained before and after each treatment period.

Vascular structure and function were measured, intravenous glucose tolerance test IVGTT and euglycemic-hyperinsulinemic clamp were performed, and adipose tissue and skeletal muscle biopsies were obtained after each treatment period.

No difference in total cholesterol, triacylglycerol, HDL cholesterol, anthropometry, blood pressure, pulse wave velocity or vascular structure could be found.

In males, none of these parameters was influenced by omega-3 supplementation. Daily supplementation with omega-3 LCPUFA capsules to obese adolescents increases serum, skeletal muscle and adipose tissue omega-3 LCPUFA concentration, improves vascular function and lowers the degree of inflammation.

It also improves glucose and insulin homeostasis in obese girls without influencing body weight. Since the identities of leaness-promoting bacteria are unknown, we tested an alternative strategy: genetically engineering gut bacteria to secrete mediators known to reduce fat intake.

N-acyl-phosphatidylethanolamines NAPEs are normally synthesized in the small intestine and their metabolites, N-acyl ethanolamides NAEs , increase satiety and decrease food intake.

We transformed the probiotic E. Four groups of C57BL6 mice 10 mice each received one of four treatments in their drinking water: no additive untreated , 0.

All groups were also fed a high-fat diet ad libitum for 8 weeks. Koalin consumption, a measure of gastric distress in mice, was similar in all four groups.

We then stopped treatment of drinking water while continuing high-fat feeding for 4 additional weeks. Post-treatment body weight gain for mice previously administered pAT-EcN was 1.

These findings suggest that consumption of probiotics engineered to express NAPE may be a useful treatment strategy for obesity.

Dietary n-3 polyunsaturated fatty acid regulation of adipokines and inflammatory mediators in adipocyte-macrophage paracrine interactions in vitro De Boer, Anna A; Robinson L.

University of Guelph, Canada In obesity, paracrine interactions between adipocytes and infiltrating macrophages in adipose tissue generate inflammation and related complications.

Similar results were found in the trans-well system, although in all fatty acid groups, adipokine secretion was nearly two-fold lower from the trans-well co-culture, emphasizing the importance of direct adipocyte-macrophage contact in paracrine interactions.

The trans-well co-culture system allowed for isolation of adipocytes to measure mRNA expression of pro-inflammatory mediators.

Overall, these data demonstrate that long-chain n-3 PUFA can decrease pro-inflammatory adipokine secretion and mRNA expression of various pro-inflammatory mediators and thus may provide a beneficial strategy to reduce inflammation in an obese state characterized by macrophage infiltration into adipose tissue.

Ouwehand, J. Research Institute, Faculty of Psychology and Education, VU University Amsterdam, Netherlands; Department of Psychiatry and Neuropsychology, Maastricht University, Netherlands Fish consumption has shown its benefits for cognitive functioning in the elderly or children with disorders e.

Therefore an observational study in Dutch high school students aged years was executed. Fish consumption data, end term grades, scores on the Amsterdam Vocabulary Test, and scores on the Youth Self-Report were collected.

Results revealed that Thus, our findings suggest that irrespective of sex, age, and educational track, the association between fish consumption and cognitive performance and academic achievement in adolescents consists of an inverted U-shape.

Higher fish intake was associated with more advanced vocabulary and higher end term grades. However, eating more fish than the described recommended amount seemed no longer beneficial.

The differences found between the groups e. The difference in z-score between the mg fish group and the highest fish consumption group equals 0.

This difference in fish consumption could therefore account for the difference between passing or failing. Procedure: Two groups of dams were fed during gestation and lactation with either a deficient ALA-palm diet containing minimal ALA level 0.

The present study demonstrates that ALA is a very potent inhibitor of the apoptosis induced by the tumor necrosis factor TNF in cardiomyocytes.

Indeed, after short exposure to TNF, survival cascades are promoted in cardiac cells, while a long-lasting cytokine stimulus causes apoptosis.

ALA pre-treatment inhibits the onset of the apoptosis in cardiomyocytes through a mechanism involving caveolae. In fact, in the presence of ALA, caveolin-3 expression is enhanced and the internalization of the TNF receptor, located into the caveolae, is inhibited determining the abortion of the apoptotic vs.

Hagel, D. Werner, B. Chiapinelli, N. Afshordel, S. Eckert, D. Juan, N. Bazan Dept. In case of a deficit of antioxidants and antioxidant cellular mechanisms the high turnover of oxygen results in the production of reactive oxygen species and ensuing damage of essential biomolecules.

Those deleterious effects accumulate especially in differentiated tissues like the brain. As a major consequence, perturbations of the energy metabolism including mitochondrial dysfunction culminate in functional deficits.

With the increasing average life span of humans, age-related cognitive disorders such as Alzheimer disease AD are a major health concern in our societies.

Strategies for long-term prevention from mitochondrial dysfunction including sufficient supply of essential nutrients may also delay the onset of age-related neurodegenerative diseases.

Neuroprotective properties of FO were assessed ex vivo after 21 days in dissociated brain cells DBC and isolated mitochondria mito.

DHA levels were significantly lower in brains of aged mice and this deficiency was compensated by FO administration. Our findings provide new mechanisms underlying the neuroprotective actions of polyunsaturated fatty acids and identified FO as promising neutraceutical to delay age-related cerebral alterations.

Supported by: Arbeitskreis Omega-3 e. Forty children aged y were matched in pairs for age, sex and maternal education and randomly assigned to intervention or control treatment.

One group received daily a margarine enriched with either 1. The study had a parallel design and duration of 3 months.

At baseline and end of intervention, fasting blood samples were drawn and analyzed on fatty acid composition of plasma lipids and red blood cell RBC phospholipids and on concentration of blood lipids.

Baseline blood lipid concentrations were on average 0. Results on blood lipid concentration will be presented and discussed.

LCPUFA are rapidly incorporated into the microdomains of the cell membrane lipid rafts where important death and growth receptors and signals are located.

Studies from our laboratory have demonstrated that the incorporation of the DHA and EPA into lipid rafts is associated with reduced epidermal growth factor receptor and increased CD95 Fas in plasma membrane rafts.

These changes were associated with post membrane changes in the signaling pathways and cell growth and apoptosis, thereby providing possible membrane-mediated mechanisms for the effects of n-3 LCPUFA on the survival of human breast cancer cells.

The cell membrane is also the target for doxorubincin DOX or adriamycin one of the drugs of choice for treatment of highly invasive metabolically active breast tumors.

Its metabolism into proand anti-inflammatory eicosanoids e. Other bioactive lipids play key roles during inflammation.

Among them are the endocannabinoids, which consist of a fatty acid linked to a molecule of glycerol or a molecule of ethanolamine.

The resulting glyceryl-esters e. Endocannabinoids are biosynthesized on demand and are hydrolyzed rapidly to fatty acids.

While the pharmacological or genetic inhibition of cannabinoid receptors supports an anti-inflammatory role of endocannabinoids, the latter induce pro- and anti-inflammatory effects.

We believe this is related to 1 their metabolism by eicosanoid biosynthetic enzymes; and 2 their hydrolysis into arachidonic acid and the subsequent synthesis of eicosanoids.

The resulting lipidome consists of numerous bioactive lipids with either pro- or anti-inflammatory effects. Interestingly, while endocannabinoids can serve as a source of arachidonic acid, fatty acid intake modulates endocannabinoid levels in the tissues.

Recent evidence supports this functional link between arachidonic acid and endocannabinoids as they play a key role in the regulation of inflammation.

Key findings regarding the functional link between endocannabinoids and arachidonic acid will be presented.

Fatty acids, lipids and cardiovascular HDL Francis, Gordon University of British Columbia, Canada Levels of plasma high density lipoprotein cholesterol HDL-C correlate generally and directly with protection against coronary heart disease, yet the level of cholesterol itself in HDL particles is frequently a poor predictor of HDL function and protection.

HDL are thought to protect against atherosclerosis for numerous reasons, including removing excess cholesterol from cells and reducing artery wall inflammation.

No lifestyle or therapeutic maneuvers, however, so far raise HDL-C specifically enough to allow this hypothesis to be tested in humans.

Clinical trials with niacin to raise HDL-C, among other effects on lipoproteins, have had mixed results, and more definitive trials are ongoing.

Agents that raise HDL-C by inhibiting cholesteryl ester transfer protein are also being investigated for potential benefit. This presentation will review the potential beneficial actions of HDL, other markers of HDL function that may be more informative than HDL-C, and maneuvers to raise HDL that are currently available or under development Linoleic acid and inflammation: evidence based research from clinical studies Fritsche, Kevin; Guy Johnson University of Missouri, USA A systematic review of randomized controlled trials that permitted the assessment of dietary linoleic acid LA on biological markers of chronic inflammation among the healthy non-infant population was conducted.

Fifteen studies eight parallel and seven cross-over met inclusion criteria. None of the studies reported significant findings for a wide variety of inflammatory markers including C-reactive protein, fibrinogen, plasminogen activator inhibitor type 1, cytokines, soluble vascular adhesion molecules or tissue necrosis factor-alpha.

The only significant outcome measures reported for higher LA intakes were greater excretion of prostaglandin E2 and lower excretion of 2,3-dinor-thromboxane B2 in one study 1 and higher excretion of tetranorprostanedioic acid in another.

However, both authors observed that these effects were not an indication of increased inflammation. It is concluded that virtually no evidence is available from randomized, controlled intervention studies among healthy, non-infant humans to show that variations in the level of LA in the diet affects in vivo inflammation in healthy humans.

Recent evidence has called into question this mantra. Confounding influences that occur as a result of variations in the effects of specific saturated fatty acids, replacement by other macronutrients, obesity state and a myriad of lifestyle factors has called the saturated fat hypothesis into question.

An association of saturated fat intake with CVD risk has not been consistently shown in prospective epidemiologic studies. Clinical trials that replaced saturated fat with n-6 polyunsaturated fat have mostly shown a reduction in CVD events, although several studies showed no effects.

The effectiveness of replacement of saturated fat by monounsaturated fat has been called into question and replacement with a higher carbohydrate intake, notably those with a high glycaemic index, is considered inadvisable due to effects on insulin resistance and obesity.

Recent reviews have highlighted the complications in replacing saturated fat and trans-fatty acids intake with n-6 PUFA linoleic acid in controlled trials showed limited benefit and have suggested that n-3 PUFA may be responsible for the protective association between total PUFA and CVD.

Creating clear guidelines from the epidemiological and clinical trial data has been made increasingly difficult in an environment where total energy intakes have increased with the resulting global increase in obesity in all age groups.

Background: There is uncertainty regarding the efficacy of increasing n-3 long chain polyunsaturated fatty acid LCPUFA intake during pregnancy on reducing the risk of gestational diabetes mellitus GDM and pre-eclampsia PE.

Birth outcomes and prenatal complications were also assessed. Birth weight, length and head circumference z-scores also did not differ between the groups.

Harding, Peter Eck, Peter J. Using a randomized crossover design, 36 hyperlipidemic subjects consumed 3 isoenergetic diets for 28 d enriched in FXCO No change in 13C-DHA was observed between diets.

Optimized rapeseed oil naturally enriched with healthy micronutrients: a relevant nutritional approach to prevent cardiovascular diseases.

INRA, France Rapeseeds are naturally rich in cardioprotective micronutrients but refining leads to substantial losses either by physical removal or by chemical reaction such as isomerisation.

We aimed to investigate the cardioprotective properties of this Optimized oil. In conclusion, reasonable intake of an Optimized rapeseed oil resulting from innovative refining processes and naturally enriched in cardioprotective micronutrients represent a relevant nutritional approach to prevent the risk of cardiovascular diseases by improving the cholesterol profile and reducing LDL oxidation.

Objective: The objective was to evaluate the effect of maternal omega-3 LCPUFA supplementation compared to a placebo in pregnancy on infant and child visual and neurological development.

Human randomised control trials that supplemented the maternal diet with omega-3 LCPUFA during pregnancy or pregnancy and lactation and assessed either visual or neurodevelopment of the offspring were included.

The quality of included trials was assessed with set criteria and results of eligible trials were compared in meta-analyses when possible Results: No clear differences in standardized psychometric test scores were observed between groups.

At no other age was there a difference between the groups in any psychometric measure of cognition although LCPUFA-supplemented infants had better eye and hand coordination MD 6.

Due to a variety of visual development assessments it was not possible to combine outcomes of different studies in a meta-analysis.

Conclusion: The evidence does not conclusively support or refute that omega-3 LCPUFA supplementation in pregnancy improves visual or cognitive development.

V; Rubia, K. Objectives: To investigate: 1. The supplementation ERP study, however, showed no significant effect of fatty acids intervention.

Furthermore, significant relationships were observed between baseline levels of fatty acids and ERP components in both HC and the ADHD groups, suggesting the involvement of fatty acids in the neural activity of brain function.

A century of change in linoleic acid: Endocannabinoids, obesity and addiction Hibbeln, Joseph R. Alvheim National Institute on Alcohol Abuse and Alcoholism, USA Suppressing hyperactive endocannabinoid tone is a critical target for reducing obesity and may reduce other disorders of satiety including alcohol misuse.

Here we posited that excessive dietary intake of linoleic acid LA , the precursor of AA, would induce endocannabinoid hyperactivity and promote obesity.

These animal diets modeled 20th century increases of human LA consumption, changes that closely correlate with increasing prevalence rates of obesity.

Similar patterns of increasing LA consumption and alcohol consumption are evident in the 20th century.

Breast cancer risk biomarkers are associated with dietary intake and tissue content of n-3 polyunsaturated fatty acids PUFA Hidaka, Brandon H.

Harvey, Debra K. Sullivan, Jennifer R. Klemp, Susan E. Carlson, Bruce F. Kimler, Carol J. Methods: Breast tissue was acquired by random periareolar fine needle aspiration from 74 women.

Breast epithelial cells were assessed for cytomorphology and proliferation Ki immunochemistry , which are validated biomarkers for breast cancer risk.

Subjects with atypia consumed less n-3 PUFA: median of 0. A lower ratio of breast TAG nn-6 0. Both lower n-3 intake and tissue content were associated with biomarkers of breast cancer risk.

Impact of n-3 supplementation on fatty acid composition of erythrocytes, plasma, and breast tissue in women at increased risk for breast cancer Hidaka, Brandon H.

Kimler, Brian Petroff, Carol J. Here we report the effect of supplementation and withdrawal on PL and TAG composition of erythrocyte, plasma and breast.

We obtained blood at 0, 6, and 6. Statistical analysis was performed using two-sided Wilcoxon signed rank test. Conclusion: LovazaTM increases the n-3 content in erythrocytes, plasma, and breast.

Some preliminary research indicates interrelationships of blood brain barrier and endothelial dysfunction in other neurodegenerative diseases.

In current study, we have measured normalization of whole blood viscosities in post-stroke patients using scanning capillary tube viscometer.

Management and treatment protocols were determined by red cell lipid analysis of patients blood at Johns Hopkins, Peroxisomal Diseases Laboratory.

Essential fatty acid EFA restoration, EFA balance and removal of oxidized lipids were determined in preparations of oral and intravenous of phosphatidylcholine, glutathione, Subtilisin NAT, eicosapentaenoic acids and methylation factors to decrease whole blood viscosity, increase RBC deformability and initiate reperfusion of post-ischemic conditions resulting from CVAs.

Results: We have previously shown that the use of oral and IV lipids facilitated stabilization of decreased whole blood viscosity and restored microperfusion in several dozen subjects.

This study suggests a correlation of whole blood viscosity and restoration of microcirculation with resolution of post-stroke neurological deficits.

This WBV normalization corresponds to marked clinical improvement in our subjects within the first 3 months of intravenous lipid therapy.

Conclusions: We have documented significant clinical neurological improvement in our subjects along with marked normalization of RBC lipids and hemorheology via laboratory analysis following three months of an oral and intravenous lipid regime.

Why do cancer cells over-express fatty acid synthase? Hopperton, Kathryn E. C Archer, R. P Bazinet University of Toronto, Canada Background: Fatty acid synthase FAS is over-expressed in many human cancer cells even in the presence of pre-formed fatty acids supplied by the medium.

Inhibition of FAS initiates apoptosis in cancer cells and decreases tumorigenesis in vivo, suggesting that FAS plays an essential role to cancer growth and survival.

Hypothesis: Cancer cells utilize endogenously synthesized fatty acids differently than those supplied exogenously, and so have a specific requirement for endogenously synthesized fatty acids.

Total lipids were extracted from the cells and culture medium and radioisotope incorporation into total lipids, cellular lipid classes, phospholipid classes and cholesterol was measured using standard chromatographic techniques and liquid scintillation counting LSC.

HPLC revealed that endogenously synthesized and exogenously supplied fatty acids are primarily palmitate, palmitoleate and stearate.

Analysis of the culture medium revealed that the cancer cells secrete endogenously synthesized fatty acids at 3 fold higher levels than non-cancer cells.

Comparison of cancer and non-cancer cells revealed that cancer cells esterify proportionately less fatty acid to phospholipid and produce over 2 fold more choline glycerol phospholipid than non-cancer cells.

Conclusion: These results suggests that FAS over-expression does not fulfill a requirement for endogenously synthesized fatty acids in cancer cells as these fatty acids are not used for unique functions within the cell.

In addition, a portion of endogenously synthesized fatty acids are excreted, suggesting that they are produced at higher levels than needed to support proliferation.

Chen, Gonzalo M. Rivera, David N. McMurray,Robert S. N-3 polyunsaturated fatty acids PUFA [e. We have previously shown that n-3 PUFA attenuate events critical for T cell activation, including localization of F-actin to the immunological synapse IS.

Since the second messenger phosphatidylinositol- 4,5 -bisphosphate PI 4,5 P2 resides in membrane lipid raft domains and DHA can alter the size of rafts, we hypothesized that PI 4,5 P2 and downstream F-actin remodeling are perturbed by the incorporation of n-3 PUFA into the plasma membrane, thereby suppressing T cell activation.

Impact of human milk and structured lipids on lipoprotein lipids in infants Innis, Sheila M University of British Columbia, Canada The mammary gland has unusual pathways of lipid synthesis that result in truncation of fatty acid synthesis at a carbon chain length of 14 or lower, and uptake of palmitic acid from maternal plasma to maintain a relative proportion of in human milk fatty acids, regardless of the maternal diet.

Triglyceride TG synthesis is also unusual, and involves preferential positioning of at the sn-2 centre carbon of the TG glycerol backbone, with n-9, n-6,n-3 and medium chain fatty acids directed towards the TG glycerol sn-1,3 positions.

Much of the interest in milk TG structures has focused on intraluminal events. Plasma lipoprotein lipids were compared between infants randomized to be fed formula containing structured TG enriched in 2palmitate or from palm olein, and to breast-fed infants at 60 and days of age.

Parallel studies enabling access to tissue lipids were done in piglets fed similar formula. The chylomicron TG of breastfed infants and infants fed formula with snpalmitate showed retention of sn-2 palmitate TG species.

Higher , but lower n-9 and n-6 in plasma monoglycerides of breast-fed infants suggests the milk TG structure may influence tissue fatty acid delivery, with preferential delivery of unsaturated fatty acids to extra-hepatic tissues, with retention of saturated monoglyceride products of lipoprotein lipase.

The TG structure and fatty acid composition also impacted the liver TAG and cholesterol, and tissue fatty acids in animals. The analyses of lipoprotein lipid, monoglyceride and fatty acids in plasma indicates that human milk TAG may be specifically organized for targeted delivery of not only which but how fatty acids are delivered to developing infant tissues.

In recent years, non-fasting triacylglycerol TAG concentrations have emerged as a clinically significant cardiovascular disease CVD risk factor, with hazard ratios of in the highest versus the lowest levels of non-fasting TAG.

Given the strength of these associations are comparable to those of low density lipoprotein cholesterol an established CVD risk factor ; there is considerable interest in understanding the independence of the association, and causality of TAG in CVD.

The postprandial TAG response has been shown to be highly variable between individuals, with the apolipoprotein APO E epsilon genotype likely to be an important genetic determinant as a result of the significant role apoE plays in lipoprotein metabolism.

However, the majority of information regarding the effects of dietary fats on lipid levels in this genotype group has been derived from studies performed in the fasting state.

Since both the amount and type of fat given in a meal has been shown to influence the magnitude and duration of the postprandial lipaemic response, little is known about the independent and interactive impact of APOE genotype.

An overview of the relationship between non-fasting TAG, dietary fat and APOE genotype will be presented; together with recent findings from our group which suggest that dietary fat manipulation may be a more important modulator of the subsequent postprandial TAG response than APOE genotype.

Ruminant trans vaccenic acid decreases fasting and post-prandial hypertriglyceridemia by reducing both hepatic and intestinal TG secretion and associated genes in a rat model of the metabolic syndrome Jacome-Sosa, Miriam M.

Both fasting and non-fasting post-prandial hypertriglyceridemia are risk factors for cardiovascular disease CVD and VA has been shown to decrease fasting hypertriglyceridemia in several pre-clinical animal models.

However, the mechanistic action by which VA exerts its hypotriglyceridemic benefits remains unclear. The objective of this study was i to evaluate the effects of VA on both intestinal fed state and hepatic fasting state TG secretion and ii to profile intestinal and hepatic gene expression using the JCR:LA-cp, a rat model of the Metabolic Syndrome MetS.

Hepatic TG secretion was assessed during fasting conditions whilst intestinal TG secretion was assessed after an oral gavage of [3H] triolein in olive oil following lipoprotein lipase inhibition.

Gene expression data suggests opposing transcriptional control in the liver and intestine as a consequence of VA supplementation. We propose that VA supplementation may contribute to improving fasting and post-prandial hypertriglyceridemia during conditions of MetS and reduce CVD risk.

Epidemiologic studies on the intake of ruminant trans fatty acids and the risk of CVD Jakobsen, Marianne Uhre Department of Public Health, Aarhus University, Denmark Observational epidemiologic studies have shown a higher risk of coronary heart disease CHD to be associated with the intake of trans fatty acids Mozaffarian et al.

Trans fatty acids arise either from industrial hydrogenation of vegetable oils, or from hydrogenation of unsaturated fatty acids in the rumens of ruminants.

As a result of biohydrogenation, meats and dairy products from cows, sheep, and other ruminants contain trans fatty acids.

The sources of industrially produced trans fatty acids are fast foods, bakery products, package snack foods, margarines, and crackers.

Overall, the evidence from observational studies suggests that higher CHD risk is related to the intake of trans fatty acids from industrial sources rather than trans fatty acids from ruminant sources Mozaffarian et al.

Observational studies on the intake of trans fatty acids from ruminant sources and the risk of CHD were reviewed.

The association between the intake of trans fatty acids from ruminant sources and the risk of CHD has been investigated in several observational studies.

Among the case-control and follow-up studies, one study Pietinen et al. In a cross-sectional study Bolton-Smith et al. In summary, observational studies suggest that the intake of trans fatty acids from ruminant sources is not associated with the risk of CHD within the range of intake in the general population.

However, these data do not exclude the possibility that higher intakes than the amounts actually consumed could have adverse effects.

Red blood cell omega-3 fatty acid levels and neurocognitive performance in deployed U. Methods: Servicemembers with mild to moderate depression by the Patient Health Questionnarie-9 from two US military camps were invited to participate in this study.

A battery of validated psychosocial Pittsburgh Sleep Quality Index, and Zung Depression, Zung Anxiety, Espworth Sleepiness, and Combat Experiences scales and computerized neurocognitive tests were completed by each participant.

A drop of blood was also collected on an antioxidant-treated filter paper card and sent for HS-Omega-3 Index analysis. Conclusion: Optimal neurocognitive performance is essential during deployment.

Our finding that EF and CF were positively related to HS-Omega-3 Index suggests that improving omega-3 status through an increase in omega-3 intake may improve neurocognitive performance and confer an element of resilience to poor sleep.

Monounsaturated and high linolenic acid oils, plasma lipids and fatty acid metabolism Jones, Peter J.

Endpoint measures revealed reductions in serum lipid concentrations, including 7. Consumption of the dietary oils failed to alter whole-body fat oxidation or energy expenditure, nor lead to any changes in body composition.

No differences in plasma 13C-DHA enrichment were observed across diets. Our previous findings revealed a link between toxic exposures, a characteristic accumulation of very long chain fatty acids VLCFAs in the form of lipid rafts or ceramides, and the development of cell membrane derangement resulting in dysfunction.

In our current study we have captured visual images of toxins on the cell surface which have caused disturbances in cellular phospholipid structure and mitochondria of individual subjects, and have linked the impact of the DNA adducts toxins altering gene expression to aberrations in lipid metabolism, cellular dysfunction and alteration of the structure of phospholipids in the cell membrane characteristic to the presenting diagnosis and symptoms.

While further work remains and the microscopic significant of these correlations needs further clarification, initial biochemical and clinical results appear promising.

Radial maie study in rats confirmed neuroprotective and memory boosting effects of krill oil. In this study we expanded the work in human to study if the krill oil adminstration will improve mental perfomance.

Using double blind, randomized, placebo control trial, 45 adult Japanese men 62 - 75 years were divided into 3 groups; fish oil group, krill oil group and palcebo group.

The subjects were given 2 g of the test substance in capsule form for 12 weeks. At the end of 12 week intervention, the subjects were subjected to brain functional neuroimaging to measure 1 oxyhemoglobin concentration by near infrared spectroscopy NIRS when the subjects performed a memory task and a calcualtion task and 2 brain event related potential P None of the interventions showed any side effects.

Krill oil treatment increased the oxyhemoglobin concentration in anterior and temporal areas of the brain following memory and calculation tasks.

The increase in oxyhemoglobin concentration was much higher with krill oil than with fish oil or placebo treatment.

Depending on the task, the different areas of the brain showed increase in oxyhemoglobin concentrations, suggesting different parts of brain are involved in different activities.

P measurement is an index of overall activity of brain. The amplitudes of P wave is related to cognitive funciton while the latency of the wave is associated with the speed of information processing.

Kril oil treatment reduced the latency, indicating it improved the speed of information processing in adult males.

Serum fatty acid composition was measured by gas-liquid chromatography. Berthiaume Department of Pathology and Laboratory Medicine, University of British Columbia, Canada; Department of Cell Biology, University of Alberta, Canada Palmitoylation or S-acylation of proteins is a reversible and versatile post-translational protein modification PTM , which involves a covalent binding of a fatty acid mostly palmitic acid to free thiols of cysteine residues.

This PTM plays important functional roles in cellular processes, such as membrane anchoring of protein complexes , signaling, trafficking and protein-protein interactions.

Measurement of palmitoylation is challenging due to a lack commercially available standards, poor longterm stability of the palmitic thioester bond and lack of adequate enrichment- or sensitive enough methods for detection.

In recent collaborative efforts, we have shown that direct mass spectrometric analysis of S-acylated peptides labeled with palmitate or palmitate analogues, obtained through enzymatic digestion of palmitoylated proteins is readily possible.

Furthermore, specific release of palmitate from S-acylated sites and relabeling with stable-isotope labeled alkylating agents, such as for example deuterated Nethylmaleimide, allows for quantitative comparisons of palmitoylation extent between samples of different origin, e.

Here, we will present further examples and an overview of our new approaches towards characterisation and measurement of S-acylated proteins, employing advanced mass spectrometry.

A number of cross-sectional human studies reported negative associations between IR and tissue concentrations of n-3 PUFA, but results from human intervention studies have varied.

Besides the changes in glucocentric markers of IR, an equally important aspect of IR is the effects of insulin on lipid metabolism lipocentric markers.

DHA supplementation increased fasting plasma glucose concentration by 4. It also did not alter other indices of IR based on fasting insulin and HOMA-IR or postprandial insulin and glucose concentrations areas under curves for insulin and glucose, Matsuda index.

None of the variables changed in the placebo group. Our results suggest that lipocentric markers of IR are more responsive to DHA supplementation than the glucocentric markers.

Future studies with DHA in pre-diabetic subjects and direct measures of insulin sensitivity are needed. As DHA is readily incorporated into the phospholipids in neuronal membranes, DHA can influence not only chemical and physical properties of cell membranes but also membrane related signaling events involved in neuronal survival, proliferation and differentiation.

Our studies have indicated that DHA supplementation increases phosphatidylserine PS accumulation and inhibits neuronal cell death under challenged conditions, supporting a notion that DHA is an important neuro-protective agent.

We also found that DHA released from the membrane is metabolized to a potent synaptogenic agent, synaptamide N-docosahexaenoylethanolamide , promoting neurite growth, synaptogenesis and glutamatergic synaptic function in developing neurons as well as neuronal differentiation of neural stem cells NSCs.

Molecular and signaling mechanisms underlying DHA-mediated beneficial effects will be discussed in the context of neuroprotection, particularly under challenged conditions such as in brain injury.

Besides composition, fat quality also encompasses physical properties of lipid droplets. Compared to current infant formula, lipid globules in human milk are up to 10 times larger and coated by a phospholipid membrane.

Weight, adipocyte number, size distribution and gene expression were analysed in white adipose tissue WAT depots. Lean body mass, food intake and adipocyte number were similar in all groups.

The expression of Pref1 preadipocyte marker remained unaffected by any of the diets, illustrating comparable preadipocyte numbers.

A resulting DHA depletion has been demonstrated in PKU children and may account for detectable subtle neurological deficits that are not explained by variation in plasma phenylalanine concentrations.

DHA supplementation resulted in significantly faster visual evoked potential latencies, indicating more rapid central nervous system information processing.

In addition, DHA significantly improved outcomes in a standardized test of motor function and coordination. No changes over time were seen in aged matched healthy controls.

Since the PKU children had a good supply of the omega-3 precursor alpha-linolenic acid, these observations lead us to conclude that endogenous conversion of alphalinolenic acid is not sufficient to provide adequate amounts of DHA that support optimal function.

Since early treated PKU children are healthy, with normal fatty acid turnover, these data may indicate a need to supply some DHA to children in general.

In an ongoing multicentric study funded by the European Commission, we aim at establishing quantitative dose response between DHA supply and functional outcomes that should help defining quantitative DHA requirements in children.

Polyunsaturated fatty acids and child health: diet or genes? In the last few years, genetic association studies demonstrated that in addition to nutritional inatkes, the genetic background is highly important for PUFA composition of human blood and tissue lipids.

Recent gene-nutrition interaction studies suggest that these polymorphisms modulate the effect of dietary fatty acid intake on complex phenotypes such as cognitive outcomes and asthma risk in children.

These first results may provide the basis for future, more specific intake recommendations to achieve optimal health benefits for all children.

We present results from those recent gene-nutrition interaction studies, discuss the implications for future observational and intervention studies as well as for child health, and provide suggestions as to how this association might translate into clinical practice in the future.

Complex etiology of metabolic syndrome implies the need of treatments, which are based on multiple mechanisms of action.

Development of the syndrome could be delayed by lifestyle modifications, while both dietary and pharmacological interventions are required for the therapy.

Naturally occurring n-3 long-chain PUFA, namely eicosapentaenoic and docosahexaenoic acids Omega-3 , exert pronounced anti-inflammatory effects, act as hypolipidaemics, reduce cardiac events and may decrease the progression of atherosclerosis.

However, Omega-3 fail to improve glycaemic control in diabetic patients. Experiments in mice fed high-fat diet revealed that Omega-3 could prevent development of obesity and hepatic steatosis, while modulating liver, adipose tissue, intestine and muscle metabolism.

Importantly, Omega-3 could augment beneficial effects of other treatments. Thus, i a combination treatment using Omega-3 and a mild calorie restriction efficiently reduced body fat accumulation, while inducing a metabolic switch toward lipid catabolism in adipose tissue; and ii a combination with anti-diabetic drugs thiazolidinediones exerted additive effects in the amelioration of dyslipidaemia and insulin resistance, while preserving muscle insulin sensitivity and metabolic flexibility, and reverting insulin resistance.

Both combination treatments strongly suppressed low-grade inflammation of adipose tissue. Combination treatment using Omega-3 and a low dose of rosiglitazone reduced obesity.

These results are relevant for the prevention and therapy of obesity and its comorbiditiesatment Effect of pomegranate seed oil on the lipid matabolism in Wistar rat Kostogrys, Renata B.

CLnA has been found abundantly in some seed oils, such as Pomegranate seed oil cis9,trans,cis; C The objective of this study was to evaluate the effect of Pomegranate seed oil as a source of CLnA compared to CLA cis-9,trans on lipid metabolism in Wistar rats.

Twenty four Wistar rats were randomly assigned to four experimental groups and fed for the next four weeks. The experimental treatments had no effect on plasma TC in rats.

Additionally, Flaxseed oil significantly increased HDL cholesterol level compared to Control group 1. Additionally, the fatty acid composition in rats fed Flaxseed oil and Pomegranate seed oil was significantly changed.

In the same line, stearoyl coenzyme A desaturase SCD-1 index was changed. In rats fed Pomegranate seed oil liver's FAS gene expression tended to decreased.

In conclusion, Pomegranate seed oil improved the lipid metabolism more effectively than CLA in laboratory rats.

Department of Nutritional Sciences, Penn State University, USA Epidemiologic studies consistently demonstrate a beneficial association of increased nut and peanut consumption with coronary heart disease and sudden cardiac death.

In addition, nut consumption is inversely associated with hypertension, type 2 diabetes and metabolic syndrome. In addition, nut consumers had fewer criteria for metabolic syndrome.

C-reactive protein also was lower in nut consumers. Numerous clinical studies have provided insight about the underlying mechanisms that account for the health benefits of nuts.

Plasma triglycerides decreased in hypertriglyceridemic individuals. In addition, there is evidence that postprandial walnut consumption may enhance HDL particle functionality and promote reverse cholesterol transport.

With respect to body weight, potential explanatory mechanisms include satiety value of nuts, induction of energy expenditure and inefficient energy absorption.

Animal studies have reported beneficial effects of walnuts on reduction in breast and colorectal cancer, as well as cognitive function.

In addition to the favorable fatty acid profile of nuts and peanuts, other bioactive compounds that explain their health benefits include: macronutrients including plant protein and fiber; micronutrients including potassium, calcium, magnesium, and tocopherols; and phytochemicals such as phytosterols, phenolic compounds, resveratrol, and arginine.

Introduction: The effect of parenteral n-3 fatty acids in critically ill infants, who are at risk of infection, is not widely studied.

This study investigated the effects of parenteral fish oil on plasma lymphocyte and procalcitonin concentrations. Parenteral nutrition was administered continuously for 3 days pre-operatively and 10 days post operatively.

Pediatric risk of mortality PRISM scores were recorded on admission to the pediatric intensive care unit.

This observation suggests that an n-3 lipid emulsion containing n:3 and n:3 may suppress the inflammatory response induced by cardiopulmonary bypass and surgery, and therefore may be beneficial to critically ill infants undergoing heart surgery.

Could an apparently inconsistent relationship between n-3LCPUFA and blood pressure in children be explained by changes in anxiety?

Lauritzen, Lotte Department of Human Nutrition, University of Copenhagen, Denmark The long-chain n-3 fatty acid n-3LCPUFA research has focused on cardiovascular benefits in adults and brain development in infants, whereas potential effects in childhood has been given little attention.

We have recently made two observational studies in order to see if such an association was detected within children. However, in both 17 years-old children from the Copenhagen Birth Cohort study and in a cross-sectional study of years-old school children we found significantly higher blood pressure in those with high n-3LCPUFAlevels in their erythrocytes or whole blood.

Since we a priori assume one common mechanism behind the effect of n-3LCPUFA on blood pressure, we speculate if the apparent inconsistency could be mediated via an effect on anxiety.

In theory, calmness would give rise to a decrease in blood pressure, whereas decreased restlessness in the long run may lead to an increase in blood pressure.

Lower physical activity was observed in the fish oil-supplemented group at the 7-year follow-up and also at higher whole blood n-3LCPUFA-levels in the cross-sectional study of school children.

Furthermore, the decrease in blood pressure after three months of n-3LCPUFA-supplementation in late infancy was found to correlate with an increase in number of episodes with quiet inattention in a free play test.

We suggest that quite inattention may be interpreted as a measure of patience. N-3 Fatty Acids and Arrhythmias Lemaitre, Rozenn N University of Washington, USA In this presentation, we will review the evidence for prevention of sudden cardiac death and atrial fibrillation with n-3 polyunsaturated fatty acids.

Secondarily, we will explore available evidence on alpha-linolenic acid ALA. Animal experimental and early clinical evidence provided a compelling hypothesis that DHA and EPA have anti-arrhythmic effects.

Patient population, dose of DHA and EPA, concurrent drug therapies, comparison group, background diet, and expected effect size and power are some of the issues to consider in exploring the conflicting clinical trial results.

There are no randomized clinical trials examining the effects of DHA and EPA on arrhythmic outcomes among those without prior heart disease, and limited data on ALA and arrhythmic outcomes.

Totality of evidence will be summarized and gaps in our knowledge identified for future studies. Effects of diet-induced decreases in brain DHA content on outcomes in a rat model of juvenile traumatic brain injury Levant, Beth; Kristin L.

Russell, and Nancy E. Long-chain n-3 polyunsaturated fatty acids have been shown to have beneficial effects in a variety of models of neural injury in adult animals.

This study examined whether diet-induced decreases in brain docosahexaenoic acid DHA affect sensorimotor outcomes in a rat model of TBI in toddlers with respect to severity and persistence of effects.

On postnatal day 17, rats received a unilateral controlled cortical impact injury to the sensorimotor cortex or sham surgery.

Sensorimotor function was evaluated 1, 7, 14, 21, and 28 postinjury. These findings indicate that a diet-induced decrease in brain DHA content contributes to poorer sensorimotor outcomes after TBI in juvenile rats.

Pro-resolving mediators, resolvins and protectins in airway inflammation Levy, Bruce D. The resolution of inflammation is an active process that is directed, in part, by specialized pro-resolving mediators that are enzymatically derived from polyunsaturated fatty acids.

In health, cell-cell interactions at the onset of acute inflammation establish biosynthetic circuits for specific chemical mediators, including resolvins and protectins, that later serve as agonists to orchestrate a return of the inflamed tissue to homeostasis.

Understanding the cellular and molecular mechanisms for pro-resolving mediators in catabasis is providing new insights into tissue responses for resolution of airway inflammation in health and the pathophysiology of lung disease; as well as opportunities for therapeutic intervention.

E-series and D-series resolvins are enzymatically derived from the essential omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid, respectively.

Protectin D1 is also derived from DHA. Evidence will be presented for these representative members of a growing family of specialized proresolving mediators to demonstrate their protective actions in the regulation of airway inflammation during innate and adaptive immune responses to mucosal injury, infection and allergen.

Thomsom, Vera C. Mazurak, Catherine J. Field, M. Tom Clandinin University of Alberta, Canada Gangliosides are negatively charged glycosphingolipids that consist of a hydrophobic ceramide and a hydrophilic oligosaccharide chain bearing one or more sialic acid.

Animal studies indicate that gangliosides modulate the immune system in weanling mice and may protect against infection.

The objective of this study was to use a human epithelial cell model Caco-2 cells induced by LPS to investigate benefits of ganglioside supplementation on IBD signaling mechanisms.

Gangliosides were extracted from milk powder and used as the ganglioside supplement in cell cultures. Epithelial barrier function was examined by measuring Trans Epithelial Electric Resistance.

However, sPLA2 level in the apical and basolaterial medium was significantly increased both by ganglisode supplement and LPS treatment.

In conclusion, the present study indicates that ganglioside supplementation in cell culture may have promising potential beneficial effects on IBD by decreasing inflammatory signaling and improving epithelial barrier function.

Using a randomized crossover design, 36 hyperlipidemic subjects consumed 3 isoenergetic diets for 29d enriched in FXCO On days 28 and 29, fasting blood was collected and stored.

No actions of diet on any other FAE were observed. However, FAE do associate with energy metabolism in humans, underscoring the role of these metabolic regulators in energy pathways.

While there is evidence that ALA may have beneficial effects for various chronic diseases, it is not possible to discern whether effects are also due to conversion of ALA to eicosapentaenoic acid EPA and docosahexaenoic acid DHA.

The recent development of the delta 6 desaturase knock out D6KO mouse model has potential to shed light on the biological role of ALA.

Thus, the loss of this enzyme enables the isolation of ALA effects independent of its conversion. Growing evidence suggests that essential fatty acids play a role in the development of non-alcoholic fatty liver disease, which is a growing health concern.

Fattier livers in D6KO mice were associated with decreased adiposity at 8 and 20 weeks. Ma and OGS to J. Possible pathophysiologic links for this association include atherogenicity of TG-rich remnant lipoprotein particles, especially in the postprandial state, increased levels of small, dense low-density lipoprotein particles in hypertriglyceridemic patients, and the association of hypertriglyceridemia with other metabolic disturbances, including insulin resistance, inflammation and hypercoagulation.

In recent years the prevalence of hypertriglyceridemia has increased markedly in North America, in parallel with the rising incidence of obesity.

Despite several decades of research on lipid-altering drug therapies, no large-scale, prospective outcomes trial has been completed to evaluate the efficacy of lipid-altering drug therapy in patients specifically selected for the presence of hypertriglyceridemia.

The best available evidence for therapy in hypertriglyceridemic patients is from subgroup analyses of clinical outcomes trials with statins, fibrates, and omega-3 fatty acids.

These results suggest that individuals with elevated TG, along with below-average levels of high-density lipoprotein cholesterol, benefit from lipid modifying therapies.

Additional clinical events data are needed to provide a more evidence-based rationale for clinical lipid management in hypertriglyceridemic patients, and to further explore the importance of fasting vs.

Log in using OpenID. Documents Health and Medicine diseases Pregnancy. This includes those that will be presented in Plenary Session, Symposia both those invited and those selected from the submitted abstracts or as Posters.

Please note that the abstracts are listed with the presenting author first. To make matters worse, obesity and concomitantly type 2 diabetes mellitus are on the rise.

This fact portends a reversal in the last decade's positive trends in cardiovascular mortality.

Unless we change our approach to cardiovascular prevention, the world will soon be faced with devastating health issues and their attendant financial ramifications.

This lecture will focus on a more modern and effective approach to CV risk reduction. It will emphasize the superiority of lipoprotein over lipid analysis; the careful use of non-invasive imaging and biomarkers; and anthropometric evaluation as a means of risk reclassifying our patients.

It will also include case presentations to depict the integration and efficacy of this model into every day clinical practice. Why is it important to study the effects of dietary lipids on membranes?

Chapkin, Robert S. Two of the most abundant bioactive lipids enriched in fish oil, eicosapentaenoic acid EPA, n-3 and docosahexaenoic acid DHA, n-3 are capable of altering cell membrane properties and resident protein activity.

Recent evidence suggests that DHA can perturb specialized regions of the plasma membrane known as lipid rafts.

Lipid rafts are mesoscale nm , heterogeneous microdomains that are enriched in cholesterol, sphingolipids, polyphosphoinositides and saturated acyl chains.

DHA is sterically incompatible with cholesterol, which can contribute to the disruption of lipid rafts. This is noteworthy, because lipid rafts serve as signaling platforms by compartmentalizing plasma membrane proteins and lipids.

In response to stimuli, nanometer-scale domains can coalesce and display high molecular order.

Many of these lipid raft mediated processes, e. Additionally, chronic inflammation, central to the process of tumorigenesis, involves excessive cell activation, which is in part regulated by lipid rafts.

Since AA-derived eicosanoids, e. However, due to safety concerns surrounding the use of pharmaceutical agents designed to target Ptgs2 cyclooxygenase II and its downstream targets, it is important to identify new targets upstream of Ptgs2.

Therefore, we determined the utility of antagonizing membrane AA levels as a novel approach to suppressing AA-derived eicosanoids.

Overall, the knowledge obtained from mechanistic studies targeting cell membranes will provide a solid underpinning for the role of dietary lipids in the resolution of chronic inflammation and cancer prevention.

This large superfamily of heptahelical molecules comprises receptors for dopamine, serotonin, epinephrine, opioids, and cannabinoids, just to mention a few.

The proper function of GPCR is critical for all higher forms of life. We are conducting structural and functional studies on two reconstituted GPCR of class A, bovine rhodopsin and recombinant cannabinoid CB2 receptor.

The GPCR are investigated at close to functional conditions, in a fluid lipid matrix with a biologically relevant composition of lipids.

Our studies place particular emphasis on polyunsaturated lipids as found in brain. The lipid matrix both preserves structural integrity of GPCR and enhances or prevents transition into the state of the receptor that activates G protein.

I will report on adjustments of the lipid matrix to the presence of the receptor and on the influence of receptor function from lipid headgroups and hydrocarbon chains.

The composition of the lipid matrix is, perhaps, the most important allosteric modulator of GPCR function. I will also address opportunities to study receptor structure in the lipid matrix at close to functional conditions by solid state NMR.

Cardiac Metabolism, University of Maastricht, Netherlands Transport of fatty acids is regulated by membrane fatty acid transporters, e.

In recent years common genetic variants of these proteins have been identified and were found to associate with circulating lipid profiles and metabolic phenotypes.

For instance, subjects with CD36 gene variants that result in a lower CD36 expression level were found to be less susceptible to the metabolic complications of obesity.

Likewise, common variants of the liver-type FABP were reported to influence insulin resistance and type 2 diabetes.

In view of the still emerging functions of these fatty acid-binding proteins, such as the role of CD36 in fat taste perception and that of CD36 and cytoplasmic FABPs in lipid signal transduction and inflammation, common gene variants are expected to contribute to individual variability in these parameters.

These new developments as well as our current understanding of the underlying molecular mechanisms will be discussed in this lecture. Division of Metabolism, Endocrinology and Nutrition, Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, WA The accumulation of cholesterol by artery wall macrophages plays a critical role in atherosclerosis, the leading cause of cardiovascular disease.

HDL has been proposed to become dysfunctional in subjects with atherosclerosis, but the underlying mechanisms are poorly understood.

One potential pathway involves myeloperoxidase MPO , a potent source of reactive intermediates in human artery wall macrophages. We used mass spectrometry to demonstrate that apoA-I of HDL isolated from patients established heart disease exhibits site-specific chlorination of tyrosine, a characteristic product of MPO.

University of British Columbia, Canada During stroke, neurons that are deprived of their normal substrates can show signs of structural damage to dendrites after as little as 2 min of ischemia.

Mitochondria also become depolarized within minutes after ishcemia. Mitochondrial dysfunction and the opening of the mitochondrial permeability transition pore mPTP are proposed to link ischemic ionic imbalance to mitochondrially mediated cell death pathways.

Some neurons escape damage within the penumbra. Over time weeks , surviving brain tissue is thought to compensate for regions lost to stroke.

It is generally assumed that recovery is a process that occurs over weeks and involves both the formation of new structural circuits and the alternative use of spared circuits.

Recovery after a small stroke may involve spared peri-infarct tissue with function similar to the infarct. In contrast, after a large stroke, tissue with similar function may only be found at more distant sites or regions within the unaffected contralateral hemisphere where structural remodeling can be observed.

Using a large bilateral craniotomy preparation in mouse, we show that targeted ischemia to even a single arteriole causes alterations in the patterns of sensory-evoked activity that extend beyond peri-infarct areas into somatotopic regions of the unaffected hemisphere as early as 30 min after stroke onset.

These findings suggest that existing sensory pathways are capable of redistributing activity to even the contralateral hemisphere.

To assess changes in functional connectivity after stroke, we are developing an automated approach to monitor intrahemispheric and interhemispheric functional relationships by the activation of Channelrhodopsin-2 ChR2 -expressing cortical neurons at arbitrary cortical points in transgenic mice.

To monitor regional cortical activity we employ organic voltage sensitive dyes. We extend the point stimulation to areas targeting association cortices and secondary somatosensory regions that are inaccessible to direct stimulation via the senses and could potentially contribute to reorganized circuitry.

We apply graph theory and complex network analysis to connection matrices derived from these functional maps to elucidate reciprocal connections between primary and secondary sensory areas, identify network hubs, and determine asymmetries in intracortical connectivity.

We anticipate that new approaches to both monitor and manipulate neuronal function will be important to describe how spared cortical circuits compensate for brain tissue lost to stroke.

M; Maggie Strable Departments of Biochemistry and of Nutritional Sciences, University of Wisconsin-Madison, Madison Wisconsin, USA Dietary fatty acids or fatty acids synthesized de novo in conjunction with nuclear receptors and transcription factors affect the transcription of a variety of genes.

The mechanisms by which these interactions and consequent effects of the individual class of fatty acids occur is proving to be complicated and yet it is invaluable to our understanding of the role that dietary fat can play in disease management and prevention.

We have used the stearoyl-CoA desaturase SCD mouse model to investigate the role of de novo synthesized fatty acids in the regulation of lipogenic gene expression.

Past work demonstrated that SCD1 deficiency impairs hepatic lipogenesis and protects against diet-induced obesity. To address this, we produced liver-specific transgenic mice expressing human SCD5, which preferentially synthesizes oleate n-9 , and introduced this transgene into GKO mice.

Hepatic oleate synthesis increased plasma glucose levels and largely prevented very-low-fat diet-induced weight loss.

This work suggests that hepatic MUFA are involved in regulation of lipogenesis and gluconeogenesis. Supported by NIH. Within a single generation populations that once were the focus of remedial supplementation programmes aimed at preventing malnutrition are now the focus of anti-obesity campaigns.

Many countries have passed through the 'nutrition transition' and others are rapidly progressing.

The desirability, affordability and abundance of refined vegetable oils has resulted in major changes in fat intake as a proportion of energy.

The quality and type of oils is highly variable and may be having profound health effects that have yet to be properly explored.

Despite this progress in many nations there remain large swathes of poverty where fat intakes may be marginal; creating a low-energy density in diets that compromises children's ability to ingest sufficient energy and potentially impairing the absorption of fat-soluble vitamins.

Essential fatty acid intakes are frequently compromised in pregnancy and young childhood, though there is great heterogeneity among studies.

Some of this heterogeneity may be caused by methodological issues, particularly in respect of accurately assaying the minor components of fatty acid profiles such as the long-chain PUFAs, and international ecological studies using standardised methodologies would be highly desirable.

Lipid-based nutrient supplements LNS provide a particularly suitable vehicle for enhancing the essential fatty acid itakes of the most at-risk mothers and children and the many on-going research challenges will be summarised.

The Role of Highly Unsaturated Fatty Acids in the Health and Disease of the Retina SanGiovanni, John Paul NEI,National Institutes of Health, USA The presentation will include: 1 an overview of extant work characterizing the capacity of diet-based fatty acids, their precursors, and metabolites to alter retinal structure and function; 2 discussion of a genomic systems-based approach to investigate relationship of receptors, transporters, enzymes and hormones impacting or impacted by these molecules in the context of pathogenesis of eye diseases manifesting neovascular and neurodegenerative components; and, 3 commentary on promising venues for development of preventive and therapeutic applications identified via the systems-based approach.

New endogenous mechanisms involved in the resolution of acute self-limited inflammatory exudates have provided insight into the control of both host defense and local acute inflammation.

Using a systems approach coupled with lipid mediator LM -metabololipidomics that we introduced, permitted the identification of several new families of potent local acting bioactive lipid-derived mediators in resolving exudates CN Serhan et al Nature Immunology This presentation shall update new advances on the biosynthesis and functions of the founding members of this novel genus of specialized pro-resolving mediators SPM and their roles as agonists of resolution.

The SPM include 3 families of chemical mediators: resolvins, protectins and the most recent addition, maresins from macrophages.

These are local autacoids biosynthesized in resolving exudates from essential omega-3 fatty acids n-3, EPA and DHA that possess potent multi-pronged anti-inflammatory, pro-resolving, reduce pain and microbial clearance actions in animal models.

Low dose aspirin also triggers production of endogenous chiral epimers from certain of SPM pathways that have to be proven bioactive and stimulate resolution.

Many other research groups worldwide now confirm endogenous formation of resolvins and protectins and their organ-protective roles and the first Rv is currently in human clinical trial.

For example, SPM have potent actions in murine ischemic renal injury, obesity-induced insulin resistance and liver disease, murine colitis and arthritis, as well as reducing pain.

These findings change the old concept that resolution of inflammation is a passive process. Together, they indicate that natural resolution pathways may underlie many prevalent diseases associated with uncontrolled inflammation and open the potential for resolutionbased therapeutics.

Triglyceride Digestion and Transport Tso, Patrick The focus of my talk will be on the digestion and absorption of dietary biliary lipids in the gastrointestinal tract, and the physiology of this event.

The digestion of dietary triacylglycerol TG begins in the stomach and continues in the intestinal lumen. Both gastric lipase and pancreatic lipase contribute to its digestion.

Following this initial breakdown of dietary TG, the hydrolytic products, monoacylglycerols MG and fatty acids FA , are solubilized in micelles and taken into the enterocyte by both passive as well as carrier mediated processes.

The importance of the unstirred water layer to the uptake of TG digestion products, as proposed by Dr.

John Dietschy, will be described. I will also focus on the uptake of cholesterol by the enterocytes, via the NPC1L1 transporter.

Following uptake into the enterocute, MG and FA are transported from the apical membrane to the endoplasmic reticulum, and re-esterified to form TG involving various enzymes.

I will also focus on the mechanism of chylomicron formation in the enterocytes, and the role of the microsomal triglyceride transfer protein in regulating the process of chylomicron formation.

Additionally, the trafficking of chylomicron particles from the endoplasmic reticulum to the Golgi apparatus will be described, as well as the process of chylomicron exocytosis and how they journey to the lacteals.

I plan to conclude the talk with a discussion of the role of various apolipoproteins in intestinal lipid transport by the enterocytes and how the conscious lymph fistula mouse model has contributed to our knowledge of the subject.

This lecture will examine the relationship between fatty acid composition and immune function, evaluate the influence of ageing on responsiveness of the immune system to n-3 polyunsaturated fatty acids PUFA , describe the role of lipid rafts in immunomodulation by fatty acids, highlight advances in eicosanoid biology, and describe emerging receptors as targets for action by fatty acids.

Hess, Manabu T. Among the most critical developments in this process is the biogenesis of an organelle unique to sperm, the acrosome, whose construction is dependent on stage-specific vesicular trafficking and membrane fusion events.

Deficiency in docosahexaenoic acid DHA was recently shown to result in a failure of acrosome biogenesis; however a role for DHA in membrane fusion has yet to be defined.

Similarly, we show by immunohistochemistry that the intracellular localization of acrosin a cargo protein of proacrosomal vesicles is normally distributed in early Golgi-phase spermatids, but in subsequent phases of spermiogenesis is dispersed throughout the cytosol in an abnormal punctate pattern.

Further, membrane fusion proteins syntaxin2 and VAMP4 displayed aberrant accumulation throughout spermiogenesis; and endoplasmic reticulum cisternae, as well as smaller transport vesicles, were present in excess on the cis-face of the Golgi, each suggestive of impaired intracellular transport or fusion.

Modulation of normal rat colon mucosa highlighted the differential effects of fish and borage oils on certain lipid and FA parameters.

ACF formation was significantly enhanced by fish oil, whereas borage oil counteracted this effect.

However, the efficacy of the intervention appears to be determined by the respective stage in carcinogenesis. S, and Anderson R.

We used a skin-specific promoter to drive the expression of ELOVL4 protein thereby generating animals with global Elolvl4 deletion except in the skin.

The skin rescued mice are runts, have defects in eyelid opening, and die within the first three weeks from birth.

This regulation extends to the sub-cellular compartments that make up the cellular architecture. Moreover, lipids help recruit proteins to specific locations and maintain their function.

Determining spatiality at the subcellular level how the lipid composition varies is therefore very important in terms of understanding the role sub-cellular compartmentation plays in regulating cellular metabolism.

To demonstrate this approach this study reports a comprehensive analysis of the subcellular proteome and lipidome of a hepatoma cell line FaO and its utility for monitoring sub-cellular changes associated with Non-Genotoxic Carcinogens NGCs exemplified by Mono 2-ethylhexyl phthalate MEHP.

A self-generating density gradient was used to partially separate organelles into individual fractions. Fractions were selected based on their profile of proteins, measured by western blotting.

Distributions were then determined by isobaric mass tagging, LC-MS and multivariate data analysis, based on proteins with known organelle locations.

This analysis of enriched organelle fractions identified numerous lipid species, whose type and concentration varied between different organelles.

Following MEHP treatment, changes were seen in the observed distribution and concentration of the lipids including PtdEtn and PtdIns throughout the gradient, supporting the hypothesis that the some of the changes in the lipid profiles, due to NGCs, are a result of induced organelle proliferation.

Here we present a rapid few seconds , real time method to analyze the fatty acid profiles in food and biological samples.

To illustrate the potential of this approach we analyzed lipid profiles of edible oils e. Samples were swiped on a capillary and placed near the mass spectrometer ion source.

Lipids were ionizated by DART, separated by ion mobility msec and mass analyzed by the time-of-flight mass analyzer. This generated 3D maps drift time, exact mass, and intensity of the sample composition at the molecular level.

Our approach of analysis is suitable for the rapid screening of various bioactive lipids, e. Potential applications include fingerprinting of biological phenotypes and comparative lipidomic analysis in the areas of personalized medicine, disease diagnostics and food analysis.

Consumption of a diet high in saturated- and trans- fatty acids increases risk of cardiovascular disease. However, consumption of the dietary trans fatty acids conjugated linoleic acids CLA may protect against cardiovascular disease and improve platelet function.

Many issues relating to the potential mechanism of protection are unknown. Platelet proteins from washed human platelets were separated in a total of protein spots using 2-dimensional gel electrophoresis.

Pathway analysis based on KEGG pathways revealed that the majority of these proteins was involved in regulation of the cytoskeleton and platelet structure, or receptor activity, signalling and focal adhesion.

These proteins, or indeed downstream proteins or metabolites, could be candidate biomarkers to measure the efficacy of fatty acids on platelet function in future nutritional intervention studies.

In the present study we fed Zucker rats with 0. In addition, the decreased ratio was associated to a lower deposition of ectopic fat in liver and heart, plasma NEFA, glycemia and insulin resistance.

We may conclude that endocannabinoid balance between visceral and subcutaneous adipose tissues is crucial for body fat homeostasis and low doses of dietary n-3PC are able to affect significantly this balance and significantly improve metabolic syndrome in obese zucker rats.

University of Western Australia, Australia Background: Overweight people are at risk of developing heart disease due to their predisposition of also having high blood pressure, lipids and glucose levels.

The cytochrome P metabolites of arachidonic acid are important regulators of vascular function and homeostasis. This study examined metabolism of arachidonic acid by the cytochrome P epoxygenase that leads to formation of 4 epoxyeicosatrienoic acid EET regioisomers.

EETs are vasodilators, and inhibit platelet aggregation. Their actions are attenuated by metabolism to dihydroxyeicosatrianoic acids DHETs by soluble epoxide hydrolase.

Their possible contribution to cardiovascular risk has not been assessed in overweight humans. Results: The volunteers were aged Plasma DHETs were not different between the groups Platelet DHETs were not different between the groups 0.

Conclusions: The increase in plasma EETs in the MetS may be a homeostatic response to elevated blood pressure or increased circulating vasoconstrictors that have been linked to insulin resistance in these subjects.

The reduced platelet EETs levels may be of relevance to increased platelet reactivity and aspirin resistance that has been described in subjects with the metabolic syndrome.

Litmanovitz, K. Davidson, A. Eliakim, R. Regev, T. Dolfin, Y. Lifshitz, D. Contrary, palmitic-acid in the sn-1 and sn-3 positions, the predominantly fat composition in regular infant formulas, is hydrolyzed by pancreatic lipase, resulting in free palmitic-acid that forms poorly absorbed complexes with calcium, also associated with lower bones calcium deposition and abdominal discomfort.

Anthropometrics and bone SOS by quantitative ultrasound Sunlight Omnisense were measured at randomization, and at 6 and 12 weeks postnatal.

Before each visit parents filled a three days report on infant feeding, stool characteristics and crying. Results: There were no significant differences in anthropometrics at randomization and at 12 weeks postnatal.

Infants in the InFat group had less episodes of crying per day and significant decrease in daily crying compared to Control group.

Conclusion: The consumption of InFat formula by term infants for 12 weeks had beneficial effects on bone SOS compared to regular Control formula and was most similar to the breastfed group.

Pipingas, A. Z Ament, Z. Swinburne University of Technology, Melbourne, Australia Background: Recent evidence suggests that, although only present in low quantities in the brain, eicosapentaenoic acids omega-3 fatty acid EPA , enhances early visual cortical processing measured with multifocal visual evoked potentials Bauer et al.

However, while docosahexaenoic omega-3 fatty acid DHA has been shown to increase neural activity during a sustained visual attention task McNamara et al.

Supplementations were administered using a double-blind, crossover design, with a day washout period between the two supplementation periods.

Participants were scanned at Baseline prior to supplementation , and after each day supplementation period. Reaction times and response accuracy were recorded.

Results: The EPA-rich supplementation was associated with a reduction in functional activation in the anterior cingulate cortex ACC when compared to Baseline.

Conclusions: Reduced brain functional activation, coupled with faster reaction times during a Stroop Color Word Interference Task suggests a mechanism of improved neural efficiency following a day EPA-rich supplementation.

Effects of iron and n-3 fatty acid supplementation, alone and in combination, on cognition: a randomized, double-blind, placebo controlled intervention in iron-deficient South African school children Baumgartner, Jeannine; CM Smuts, L Malan, MB Zimmermann Centre of Excellence in Nutrition, North-West University, Potchefstroom, South Africa; Laboratory of Human Nutrition, Institute of Food, Nutrition and Health, Switzerland Background: Little is known about the combined effects of iron and n-3 fatty acid n-3 FA supplementation in children suffering from both deficiencies.

Objective: We investigated whether providing iron and a mixture of docosahexaenoic DHA and eicosapentaenoic acid EPA , alone and in combination, to children with iron deficiency and poor n-3 FA intakes will improve cognitive performance.

No effects on cognition were found in the non-anaemic children. Conclusions: Our findings suggest that iron supplementation may improve verbal and non-verbal learning and memory in children suffering from anaemia.

Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, School of Medicine, USA The significance of the selective enrichment in omega-3 essential fatty acids in the nervous system has remained, until recently, incompletely understood.

We found that NPD1 is promptly made in response to oxidative stress and brain ischemia-reperfusion, and in the presence of neurotrophins.

We will present the following studies: 1 DHA i. Neurological function was evaluated on up to 7 days after MCAo. DHA improved behavioral scores and reduced cortical , subcortical and total infarct volumes 7 days after stroke.

In addition, DHA reduced microglia infiltration and increased number of astrocytes and neurons. Then we performed the total chemical synthesis of this molecule and tested the novel AT-NPD1 by iv 1 hr after 2h middle cerebral artery occlusion in rats.

Brain edema, computed from T2WI in the cortex penumbra and striatum core , was elevated in the saline group. In conclusion NPD1 targets neuroinflammatory signaling at various check points as well as modulates apoptotic cascades and other forms of cell death in turn promoting homeostatic regulation of neuronal circuitry integrity in experimental stroke.

In this talk, I will review how polyunsaturated fatty acids PUFA enter the brain, and the mechanisms that regulate their concentrations within brain phospholipids.

Whereas little evidence exists to support the incorporation of PUFA from lipoproteins into the brain, the incorporation rates of arachidonic and docosahexaenoic acid from the plasma unesterified pool into brain phospholipids closely approximate independent measures of their consumption rates by the brain.

Thus, with the use of radiolabelled fatty acids, it is possible to image and quantify their entry and uptake into the brain in rodents and, with positron emission tomography, in humans.

Upon entry into the brain, certain PUFA are highly conserved with extensive recycling within phospholipids, whereas others, such as eicosapentaenoic acid, are rapidly and extensively removed from the brain, in part, due to b-oxidation.

Identifying the mechanisms by which PUFA enter and are handled within the brain could lead to a better understanding of nutritional requirements for the brain as well as new therapeutic targets and novel imaging methods.

Background: Membrane phospholipid metabolism and redox regulation may be disturbed in schizophrenia.

This has entailed randomised controlled trials with either omega-3 fatty acids or redox regulators. The present study examines the effects of combining these agents.

We hypothesized that lower baseline levels of polyunsaturated fatty acids PUFA would predict more benefit from trial drugs.

Patients aged years with DSM-IV schizophrenia, schizoaffective or schizophreniform disorders were consecutively included at admission to hospital.

Results: Ninety-nine patients were included. At baseline, erythrocyte PUFA were measured in 97 subjects.

PUFA were bimodally distributed low, high. Trial drugs had clinical effects beyond psychotic symptoms, mainly in low PUFA patients.

When these agents are combined, they seem safe. Diets rich in long-chain w-3 polyunsaturated fatty acids, namely docosahexaenoic acid DHA and eicosapentaenoic acid EPA , have been shown to have many beneficial effects such as the improvement of insulin sensitivity with beneficial effects against obesity and the prevention of cardiovascular diseases.

The content and the expression of adiponectin in adipose tissues were also measured 2 to evaluate the effects of DHA and EPA and their respective oxygenated metabolites on adiponectin secretion by 3T3-L1 adipocytes.

In all three white adipose tissues subcutaneous, epididymal and retroperitoneal tissues , the adipokine content was not significantly different between mice fed the w-3 polyunsaturated fatty acid-rich diet and mice fed with the standard diet.

However, the adiponectin content was dependent on adipose tissue depot. Adiponectin gene expression was significantly increased in epididymal and subcutaneous tissues of DHA-fed mice compared to control mice.

Our studies show that DHA and EPA rapidly improved the profile of secreted adiponectin in mice and in 3T3-L1 adipocytes and suggest that this effect may be mediated by their respective oxygenated metabolites.

These data confirm that dietary intake of w-3 polyunsaturated fatty acids may be beneficial for prevention or treatment of cardiovascular and obesity-associated diseases.

Myristoylated and palmitoylated proteins in the regulation of apoptosis and metabolism revealed through proteomic Berthiaume, Luc G; Dale D.

Martin, Morris A. Kostiuk, Megan C. Yap and Erwan Beauchamp Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Canada Fatty acylation, the attachment of fatty acids to proteins, is a critical mechanism of cellular control.

It impacts virtually every aspect of cellular life. Using chemical biology, we and others recently developed approaches leading to the rapid detection, identification and characterization of acylated proteins using azido- and alkynyl fatty acid analogs.

Myristoylation is the co- or post-translational attachment of myristate to N-terminal glycine residues of proteins.

Very little is known about post-translational myristoylation and our new characterization efforts resulted in the demonstration that 15 or more post-translationally myristoylated proteins exist in various cell lines undergoing apoptosis and in the identification of 5 of these with life and death implications for the cell.

Palmitoylation, the modification of proteins by palmitate, is known as a key membrane tethering and cellular localization mechanism.

In addition, we recently identified 21 palmitoylated proteins in mitochondria, where palmitoylation had various and profound effects on the catalytic activity and function of the modified proteins, with new implications in the regulation of metabolism.

In summary, we will present several examples illustrating how chemical biology approaches using click chemistry can catalyze the discovery of new roles for fatty acids in the regulation of cell death mechanisms and metabolism.

Objective: To investigate the association between levels of polyunsaturated fatty acids PUFA in maternal whole blood at week 24 of gestation and multiple lifestyle factors.

Data on socioeconomic and lifestyle factors was obtained prospectively during visits to the research unit, and fatty acid compositions of whole blood were determined.

Covariates that were significantly associated with the dependent variable in the univariate analyses were included in a stepwise backwards elimination multivariate model with a cut-off P-value of 0.

Results: We found independent positive significant associations between all n-3 PUFA variables and high education, high income, non-smoking, and being primiparious.

The n-6 PUFA variables were not associated with any of the factors. None of the preselected PUFA variables were associated with maternal age and asthma, urban living, or gender of the child.

Thus, when analyzing associations between n-3 PUFAstatus and health, the socioeconomic and lifestyle factors that have an independent association with both blood fatty acid composition and health must be taken into consideration.

Whale blubber was part of the traditional Eskimo diet. After news ads and telephone screening, participants were assessed for inclusion by a doctor.

Marine omega-3 fatty acid intake was restricted in a two week run-in period and during the 6 week intervention period.

Urinary F2 isoprostanes were generally low though significantly increased in WO group after 6 weeks, but not compared with FO group. In conclusion; whale oil may possibly be as good an omega-3 source as fish oil, when given in equivalent medium dosage in the present short-term bioavailability study in healthy volunteers with a relatively high baseline omega-3 intake.

Information on source is uniquely retained by intrinsic stable isotope ratios, while kinetics and pool characteristics can be obtained starting with a specific enriched compound and following the transfer of label to products.

Most food plants operate with the C3 pathway, with corn using the C4 pathway. The acetate pool in animal cells has input from all sources of dietary carbon and thus reflects the mix of C3 and C4 plants in the diet.

Three examples will be presented. Carbon isotope analysis reveals that the major retinal saturated and monounsaturated fatty acids originate with corn, while DHA and n-3 both originate with C3 plants that were likely to be incidental feed components.

Steroid hormones and their metabolites reflect the dietary mix of C3 and C4 plants, with input from preformed dietary cholesterol.

These techniques were instrumental in establishing the biosynthetic efficiency for the conversion of precursor PUFA linoleic and linolenic acids to highly unsaturated fatty acids in pregnant and neonate non-human primates and humans.

Diets of the treatment groups were supplemented with chia or flax after 8 wk on H diet for a further 8 wk.

Compared to the H rats, ALA-supplemented rats had improved insulin sensitivity and glucose tolerance, reduced visceral adiposity, decreased hepatic steatosis, reduced cardiac and hepatic inflammation and fibrosis without changes in plasma lipids or blood pressure.

Stearoyl-CoA desaturase-1 inhibition was shown as an increase in the substrate concentrations together with depletion of products in the heart, liver and the adipose tissue of ALA-supplemented rats.

The Ctrans-7 was preferentially stored in the adipose tissue; the relatively inert Cn-9 was stored in sensitive organs such as liver and heart and Cn-6, the parent fatty acid of the n-6 pathway, was preferentially metabolised.

Thus, ALA induces lipid redistribution associated with cardioprotection and hepatoprotection following reduced inflammatory cell infiltration.

These results strongly suggest that ALA produces pharmacological responses independent of conversion to longer chain fatty acids in inflammatory conditions such as metabolic syndrome and arthritis.

Design and methods: In an open-label randomized, controlled trial, healthy pregnant women either received a dietary intervention [supplementation with mg n-3 LCPUFAs per day and a dietary counseling to reduce AA intake] from 15th week of gestation until 4 months of lactation or followed their habitual diet.

Breastmilk fatty acid profile was analysed at 6 weeks and 4 months postpartum. Multiple regression models adjusting for relevant confounders were performed to determine the relationship between breastmilk fatty acid composition and infant fat mass assessed by skinfold thickness measurements and abdominal sonography up to 1 year pp.

AA content was comparable between both groups. Conclusion: Breastmilk n-3 fatty acids appear to stimulate fat mass growth over the 1st year of life whereas AA seems to be involved in the regulation of overall growth especially in the early postpartum period.

Individuals with type 2 diabetes are at high risk for cardiovascular events. Eicosapentaenoic acid EPA -derived resolvin lipid mediators have been shown to decrease platelet activation in ex-vivo human samples.

Platelet spreading, platelet granulate content release, and platelet receptor conformational changes are all correlated with increased cardiovascular disease.

When compared to untreated controls, there was a significant decrease in the percentage of spread platelets after treatment with increasing concentrations of 17R-resolvin D1, untreated A significant decrease in spreading was also observed when both 17 R and 17S-resolvin D1 were used in combination, untreated Our results suggest that DHA-derived resolvin lipid mediators have modest anti-platelet effects as quantified by platelet cell surface markers of activation and morphological spreading evaluation in individuals with and without type 2 diabetes.

More studies should be conducted to elucidate additional anti-platelet effects of omega-3 derived metabolites. University of Manitoba, Canada Background: Arachidonic acid ARA derived eicosanoids influence renal hemodynamics, inflammation, and injury.

Methods: To investigate the effects of ALA on early obesity-related glomerulopathy and the renal eicosanoid lipidome, diet-induced obese rats with similar levels of obesity were provided with seven diets containing a wide range of ALA levels and n6:n3 ratios.

Prostanoids have been associated with later stages of renal disease and glomerulomegaly. Soy , renal HOTrE levels were 3-fold greater.

Conclusions: Novel renal eicosanoids produced in vivo with ALA enriched diets were identified. Delivery gestational age was based on ultrasound in the second trimester of pregnancy.

Weight, length and head circumference were obtained at birth. Results: Women in both groups consumed similar numbers of capsules mean 2.

DHA increased mean gestational age from Conclusion: DHA supplementation at this level is safe, Prenatal supplementation increased gestation duration, DHA status markers in mother and newborn, birth weight, length, and head circumference.

Supported by 1R01 HD The effects of ruminant trans fatty acids R-TFA have only been studied recently. Similarly, other epidemiological studies also indicated the lack of association between R-TFA intake and cardiovascular risk.

Intervention studies carried out in Canada and France were published at the beginning of the present Century. These data suggested that, at least at usual levels of consumption, there is no association between R-TFA intake and cholesterol-dependant cardiovascular risk factors, but men and women appeared to present different patterns.

To draw definitive conclusion, we conducted a meta-analysis including all the intervention studies in healthy volunteers with at least one experimental group with documented R-TFA intake.

From thirteen studies that met all our selection criteria, we extracted data from one or several groups, yielding to twenty-two observations.

Daily intakes of R-TFA ranged from 0. However, further analysis such as multivariate analysis including confounders would be relevant to confirm these results.

Trepanier, A. Domenichiello, Z. Liu, R. Bazinet University of Toronto, Canada Background: Eicosapentaenoic acid EPA is currently under investigation as a potential treatment for neurological disorders such as bipolar disorder and major depression; even though, in the brain, its function is poorly understood and the levels of EPA are fold lower than docosahexaenoic acid DHA.

Freeliving rats were infused at steady state for 5 minutes via the tail vein and blood samples were collected throughout infusion via jugular vein catheter.

After 5 minutes, rats were subjected to high-energy, headfocused microwave irradiation and brains were collected.

Preliminary results: Radioactivity in the aqueous fraction decreased significantly in MEP-treated brain compared to vehicle controls palmitate: 3.

This was accompanied by a significant increase in total lipid radioactivity of MEP-treated brains as compared to controls palmitate: 1.

Future analysis: Radioactivity in various neutral lipids and phospholipid fractions will be analyzed and the identities of radiolabeled fatty acids will be determined.

Thomas, Iris J. Edwards, Isabelle M. Berquin Departments of Cancer Biology, Biochemistry, Pathology; Wake Forest School of Medicine, USA Phospholipids are crucial components of cellular membranes as well as signaling molecules, with fatty acids at the sn-1 and sn-2 position of the glycerol backbone, and choline, ethanolamine, serine or inositol at the sn-3 position.

AKT is a serine-threonine protein kinase that plays important roles in cell growth, proliferation and apoptosis.

It is well documented that AKT activation requires its binding to phosphatidylinositol phosphates PIPs with phosphate groups at positions 3, 4 [i.

PI 3,4 P2] and 3,4,5 [i. PI 3,4,5 P3] on the inositol ring. However, it is unclear whether fatty acids at the sn-1 and sn-2 position can affect the ability of PIPs to activate AKT.

Here we show that dietary polyunsaturated fatty acids PUFA modify phospholipid structure. Our study suggests that dietary fat, through the structural modification of phospholipids, can affect the AKT signaling pathway that is critical in the development of human cancers.

However, the mechanism is not clear. We also studied the correlation between NF-KB signaling and tumor weight in rat mammary tumor.

Western blot analysis was performed on whole cells, cytosol and nuclear fractions for the NF-KB signaling protein expression.

Methods: Forty healthy participants were recruited. Pre-supplementation control : A single oral dose of 50 mg of 13C-DHA was given to the participants at breakfast, and its appearance in plasma and betaoxidation was monitored for 28 days.

A supplement 3. Post-supplement: In the last 28 days of the supplementation, a single oral dose of 50 mg of 13C-DHA was given to the participants to follow its metabolism.

Post-supplement, cumulative beta-oxidation was 1. Carlson, Carol L. Cheatham, D. Jill Shaddy, Kathleen M. Gustafson, Kathleen N.

Kannass, Caitlin C. Docosahexaenoic acid DHA , which is found in high concentration in the brain, is specifically thought to affect cognitive function.

At delivery infants were randomly assigned to formulas varying in DHA content: 0. Arachidonic acid was present at 0. Formulas were fed to 12 mo of age.

Results: Seventy of 86 infants followed over the long-term remained in the study through 60 mos. Analyses included Formula and for repeated tests Age.

Further support comes from significant progress in understanding the neurophysiology of DHA at the cellular and lipidomic levels, and in animal models of neurodegenerative disease.

Hence, there is considerable momentum reinforcing the concept of a protective effect of DHA on cognition in the elderly. Hence, there is a problem in the human studies on AD, i.

The focus of this talk will therefore be on discussing two themes that may bridge this disconnect: i human studies of DHA levels in AD brain and plasma, and ii changing DHA homeostasis in the elderly.

The emerging recognition that two important risk factors for AD, i. This abnormality is thought to be a factor for the increased tendency of blood cells of SCD patients to aggregate and adhere to vascular endothelium and subsequently precipitate vas-occlusive crisis and organ damage.

However, sickle cell patients are under oxidative stress and this could be aggravated by supplementation. Plasma alpha-tocopherol vit E , and red blood cell antioxidant enzymes and dimethy acetals marker of plasmalogen status were analysed at baseline and six-month supplementation.

Vit E was assessed in a sub-group of patients after one year. The activities of Se-GPx There was no difference in percent total dimethylacetals in CPG 0.

Plasma vit E concentration increased after one year supplementation Hence, it should be safe to supplement sickle cell patients to help ameliorate membrane abnormality and vaso-occlusive crisis.

We wanted to assess whether supplementation of omega-3 LCPUFAs increases the omega-3 LCPUFA concentration in serum, skeletal muscle and adipose tissue, improves vascular function and morphology and lowers inflammation in obese adolescents.

We also wanted to investigate effects on glucose and insulin homeostasis. Methods: 25 obese adolescents 14 females, 11 males, age The study was performed in a double blind, crossover design with 6 weeks washout period.

Anthropometry, blood pressure measurements and fasting blood samples were obtained before and after each treatment period.

Vascular structure and function were measured, intravenous glucose tolerance test IVGTT and euglycemic-hyperinsulinemic clamp were performed, and adipose tissue and skeletal muscle biopsies were obtained after each treatment period.

No difference in total cholesterol, triacylglycerol, HDL cholesterol, anthropometry, blood pressure, pulse wave velocity or vascular structure could be found.

In males, none of these parameters was influenced by omega-3 supplementation. Daily supplementation with omega-3 LCPUFA capsules to obese adolescents increases serum, skeletal muscle and adipose tissue omega-3 LCPUFA concentration, improves vascular function and lowers the degree of inflammation.

It also improves glucose and insulin homeostasis in obese girls without influencing body weight. Since the identities of leaness-promoting bacteria are unknown, we tested an alternative strategy: genetically engineering gut bacteria to secrete mediators known to reduce fat intake.

N-acyl-phosphatidylethanolamines NAPEs are normally synthesized in the small intestine and their metabolites, N-acyl ethanolamides NAEs , increase satiety and decrease food intake.

We transformed the probiotic E. Four groups of C57BL6 mice 10 mice each received one of four treatments in their drinking water: no additive untreated , 0.

All groups were also fed a high-fat diet ad libitum for 8 weeks. Koalin consumption, a measure of gastric distress in mice, was similar in all four groups.

We then stopped treatment of drinking water while continuing high-fat feeding for 4 additional weeks.

Post-treatment body weight gain for mice previously administered pAT-EcN was 1. These findings suggest that consumption of probiotics engineered to express NAPE may be a useful treatment strategy for obesity.

Dietary n-3 polyunsaturated fatty acid regulation of adipokines and inflammatory mediators in adipocyte-macrophage paracrine interactions in vitro De Boer, Anna A; Robinson L.

University of Guelph, Canada In obesity, paracrine interactions between adipocytes and infiltrating macrophages in adipose tissue generate inflammation and related complications.

Similar results were found in the trans-well system, although in all fatty acid groups, adipokine secretion was nearly two-fold lower from the trans-well co-culture, emphasizing the importance of direct adipocyte-macrophage contact in paracrine interactions.

The trans-well co-culture system allowed for isolation of adipocytes to measure mRNA expression of pro-inflammatory mediators.

Overall, these data demonstrate that long-chain n-3 PUFA can decrease pro-inflammatory adipokine secretion and mRNA expression of various pro-inflammatory mediators and thus may provide a beneficial strategy to reduce inflammation in an obese state characterized by macrophage infiltration into adipose tissue.

Ouwehand, J. Research Institute, Faculty of Psychology and Education, VU University Amsterdam, Netherlands; Department of Psychiatry and Neuropsychology, Maastricht University, Netherlands Fish consumption has shown its benefits for cognitive functioning in the elderly or children with disorders e.

Therefore an observational study in Dutch high school students aged years was executed. Fish consumption data, end term grades, scores on the Amsterdam Vocabulary Test, and scores on the Youth Self-Report were collected.

Results revealed that Thus, our findings suggest that irrespective of sex, age, and educational track, the association between fish consumption and cognitive performance and academic achievement in adolescents consists of an inverted U-shape.

Higher fish intake was associated with more advanced vocabulary and higher end term grades. However, eating more fish than the described recommended amount seemed no longer beneficial.

The differences found between the groups e. The difference in z-score between the mg fish group and the highest fish consumption group equals 0.

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