ALA, EPA and DHA differentially Modulate Palmitate-induced Lipotoxicity through Alterations of its Metabolism and Storage in C12C12 Muscle Cells

On that occasion, the two French societies dedicated to lipid science and technology, GERLI and SFEL, will combine their efforts to assist the scientific committee to establish an attractive program for the Euro Fed Lipid congress.Since few decades, incidence of obesity and type 2 diabetes (T2D) is increasing. Excessive intake of energy leads to fat overload and formation of lipotoxic compounds mainly derived from the saturated fatty acid palmitate in insulin-sensitive tissues (muscle, liver and white adipose tissue), promoting insulin resistance (IR, a well-known metabolic disorder in T2D). Supplementation with n-3 fatty acids (n-3FA) is suggested to reduce lipotoxicity and IR. We hypothesized that, according to the n-3FA used, differential and specific effects on palmitate metabolism in muscle cells will be demonstrated. C2C12 myotubes were treated with 500 µM of palmitate without or with 50 µM of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) for 16 hours and collected for measurement of membrane fluidity using diphenyl-hexatriene, ceramide content, insulin-dependent Akt protein phosphorylation (as an index of IR). The assessment of the intracellular metabolism and incorporation of palmitate into lipid fractions (triglycerides, phospholipids, diglycerides) was performed after treatment for 3 hours with [1-14C]-palmitate. As expected, palmitate-induced IR was restored by EPA and DHA supplementation whereas ALA had no effect compared to palmitate alone. EPA and DHA significantly improved C2C12 membrane fluidity compared to palmitate alone (+8.5% and +13% respectively, p<0.05). Furthermore, palmitate incorporation into the diglyceride fraction was decreased by 31 and 47% by EPA and DHA vs. palmitate, respectively (p=0.05). However, DHA significantly increased the ratio of diglycerides to total lipids vs. palmitate alone (p<0.05), whereas EPA did not. Finally, EPA was more potent to decrease palmitate-induced ceramide accumulation (+174%, p<0.05 vs. control) compared to DHA (-50% and -29% repectively, p<0.05). In conclusion and contrary to ALA, EPA and DHA treatment improved the insulin signalling pathway by differently modulating membrane fluidity and lipid and palmitate metabolism, thus demonstrating that n-3FA have different metabolic impacts on C2C12 lipid metabolism

Effets comparatifs des acides gras omega-3 (ALA, EPA, DHA) sur la sensibilité à l’insuline des cellules musculaires C2C12 dans un contexte lipotoxique

Objectifs :Etudier le rôle des ω3 sur la lipotoxicité induite par l’acide gras saturé palmitate (PAL, C16:0) dans un modèle de cellule musculaire C2C12.Identifier les effets propres de chaque w3 (ALA, EPA et DHA) à dose équivalente sur la fluidité des membranes et la réponse à l’insuline.Suivre le devenir intracellulaire du [1-14C]-palmitate en présence d’un w3 et définir les classes de lipides altérées.Rechercher les voies de signalisation impliquées dans la modulation de la réponse à l’insuline

The importance of the altricial – precocial spectrum for social complexity in mammals and birds:A review

Various types of long-term stable relationships that individuals uphold, including cooperation and competition between group members, define social complexity in vertebrates. Numerous life history, physiological and cognitive traits have been shown to affect, or to be affected by, such social relationships. As such, differences in developmental modes, i.e. the ‘altricial-precocial’ spectrum, may play an important role in understanding the interspecific variation in occurrence of social interactions, but to what extent this is the case is unclear because the role of the developmental mode has not been studied directly in across-species studies of sociality. In other words, although there are studies on the effects of developmental mode on brain size, on the effects of brain size on cognition, and on the effects of cognition on social complexity, there are no studies directly investigating the link between developmental mode and social complexity. This is surprising because developmental differences play a significant role in the evolution of, for example, brain size, which is in turn considered an essential building block with respect to social complexity. Here, we compiled an overview of studies on various aspects of the complexity of social systems in altricial and precocial mammals and birds. Although systematic studies are scarce and do not allow for a quantitative comparison, we show that several forms of social relationships and cognitive abilities occur in species along the entire developmental spectrum. Based on the existing evidence it seems that differences in developmental modes play a minor role in whether or not individuals or species are able to meet the cognitive capabilities and requirements for maintaining complex social relationships. Given the scarcity of comparative studies and potential subtle differences, however, we suggest that future studies should consider developmental differences to determine whether our finding is general or whether some of the vast variation in social complexity across species can be explained by developmental mode. This would allow a more detailed assessment of the relative importance of developmental mode in the evolution of vertebrate social systems

Cellulose, pectin and water in cell walls determine apple flesh viscoelastic mechanical properties

International audienceThe viscoelastic mechanical properties are important quality traits for fleshy fruit uses. The contribution of cell wall polysaccharides chemistry and organization on their variability was studied in six varieties of apple. Correlation between damping and storage modulus of plasmolyzed tissue distinguished better apple varieties on their viscoelasticity than fresh samples. Galactose, arabinose and uronic acids correlated positively with the storage modulus of fresh apple samples (E'(f)). These corresponded to 4-linked galactan but no specific arabinose linkage. Galacturonic acid branched on O-3 and terminal rhamnose correlated negatively with E'(f). These correlations formed two groups of fruit except for branched methyl-esterified galacturonic. Solid-state C-13 NMR spectroscopy analyses showed that E'f correlated negatively with cellulose C4 T-1 rho(H) relaxation and positively with pectin methyl esters T-HH proton diffusion. The results point to the key roles of pectin structure and hydration and cellulose microfibrils distribution on apple mechanical properties

Does Increased Abdominal obesity Depress Cardiac Function through a Change in Phospholipid Fatty Acid Composition?

National audienceBackground: High fat diets increase abdominal obesity, which is known to induce cardiomyopathy in the long term. The purpose of this study was to determine the mechanism of high abdominal adiposity-induced changes in cardiac function. Methods: Rats were fed a control diet (5% of equilibrated lipids) or a lard-enriched one (LD, 54% of lipids) for 3 months from the age of 3 months old. The fatty acid composition of cardiac phospholipids was determined and the in vivo and ex vivo cardiac function as well as ex vivo coronary reactivity were determined. The results were completed by measurements of cytosolic redox potential and mitochondrial oxidative stress. Results: LD stimulated elongases and inhibited D5- and D6- desaturases, which resulted in decreased 18:2n-6 and increased 20:4n-6 proportions in cardiac phospholipids. The augmented proportion of 20:4n-6 was responsible for an increased ex vivo coronary reactivity, since cyclooxygenase inhibition suppressed the difference. It could also explain the augmented in vivo cardiac function. However, when measured ex vivo, the cardiac function was depressed by the LD and this was associated with reduced glycolytic rate and cytosolic redox potential as well as mitochondrial oxidative stress. Conclusion: To respond to the increased energy needs related to obesity, the animals augmented their cardiac function through an accumulation of arachidonic acid. However, high fat-induced disturbances of the glycolytic pathway diminished reduced equivalents available for the glutathione peroxidase and increased the mitochondrial oxidative stress. Mitochondrial oxidative stress is known to inhibit the aconitase enzyme of the Krebs cycle and to reduce the energy production. The energy disequilibrium observed in that situation is thus probably responsible for the later cardiomyopathy occurring with type-2 diabetes

Impact differentiel des acides gras N-3, ALA, EPA et DHA sur la lipotoxicité induite par le palmitate dans le muscle

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Les parois dans les graines de légumineuses : une source de variation qui peut affecter les valeurs d'usage

National audienceLes légumineuses à graines font partie de la famille des Fabacées et recouvrent une large variété d’espèces (pois, féverole, lupin, soja, lentilles, haricots,…) dont les caractéristiques communes sont de fixer l’azote de l’air grâce à une symbiose avec des bactéries du sol, d’avoir des graines riches en protéines (taux moyen variant entre 22 et 40 %) et de produire des graines récoltées en sec pour l’alimentation (animale ou humaine). Les légumineuses à graines véhiculent l’image d’aliments sains avec des effets bénéfiques sur la santé en raison de leur complémentarité nutritionnelle avec les céréales et de leur rôle dans la prévention des maladies (maladies cardiovasculaires, diabète de type 2, obésité…). Le potentiel nutritionnel des graines de légumineuses se base sur leur niveau élevé en protéines et, en fonction des espèces, en amidon ou en lipides. Parmi les macronutriments, les graines de légumineuses contiennent également des quantités appréciables en fibres alimentaires. Toutefois, et malgré leurs avantages agronomiques, environnementaux et nutritionnels, les légumineuses à graines représentent aujourd’hui moins de 2 % de la sole française en grandes cultures contre 10% à 25% en Amérique du Nord ou en Asie. Dans le contexte actuel de transition alimentaire (ré-équilibrage alimentaire par réduction de produits « animaux », aliments riches en protéines, fibres et composés bioactifs), d’environnement et de santé (protéines, fibres), il devient nécessaire d’encourager une plus grande diversité cultivée qui permettrait de réduire significativement l’usage des intrants de synthèse et les pressions environnementales induites, de préserver la biodiversité et de favoriser la consommation des légumineuses. De nombreuses études de criblage associant des données génétiques, biochimiques (teneur en protéines, amidon, fibres, α-galactosides…) et phénotypiques (taille des graines, couleur et usages (aliment ou horticole)) ont été ou sont actuellement menées afin de caractériser des collections de légumineuses à graines (pois principalement). Toutefois, peu d’études intègrent la notion de variabilité de composition et de structure des polysaccharides de paroi, constituants majoritaires des fibres alimentaires, et dont le rôle dans la digestibilité, la stimulation du système immunitaire et la prévention des maladies est largement connu. Dans ce contexte, nous proposons d’étudier cette variabilité par des méthodes de criblages biochimique et histologique et de la coupler aux marqueurs de qualité usuels (protéines, facteurs anti-nutritionnels, morphologie des graines...) afin de sélectionner et de proposer de nouvelles lignées d’intérêt. Par la suite, l’impact de la composition et de la structure de polymères d’intérêt (polysaccharides, protéines) sur leurs usages (digestibilité, effet santé et procédés de transformations industriels) sera à évaluer

Modulation de la sensibilité à l'insuline musculaire par le DHA

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Body adiposity dictates different mechanisms of increased coronary reactivity related to improved in vivo cardiac function.

International audienceBACKGROUND: Saturated fatty acid-rich high fat (HF) diets trigger abdominal adiposity, insulin resistance, type 2 diabetes and cardiac dysfunction. This study was aimed at evaluating the effects of nascent obesity on the cardiac function of animals fed a high-fat diet and at analyzing the mechanisms by which these alterations occurred at the level of coronary reserve. MATERIALS AND METHODS: Rats were fed a control (C) or a HF diet containing high proportions of saturated fatty acids for 3 months. Thereafter, their cardiac function was evaluated in vivo using a pressure probe inserted into the cavity of the left ventricle. Their heart was isolated, perfused iso-volumetrically according to the Langendorff mode and the coronary reserve was evaluated by determining the endothelial-dependent (EDV) and endothelial-independent (EIV) vasodilatations in the absence and presence of endothelial nitric oxide synthase and cyclooxygenase inhibitors (L-NAME and indomethacin). The fatty acid composition of cardiac phospholipids was then evaluated. RESULTS: Although all the HF-fed rats increased their abdominal adiposity, some of them did not gain body weight (HF- group) compared to the C group whereas other ones had a higher body weight (HF+). All HF rats displayed a higher in vivo cardiac activity associated with an increased EDV. In the HF- group, the improved EDV was due to an increase in the endothelial cell vasodilatation activity whereas in the HF+ group, the enhanced EDV resulted from an improved sensitivity of coronary smooth muscle cells to nitric oxide. Furthermore, in the HF- group the main pathway implicated in the EDV was the NOS pathway while in the HF+ group the COX pathway. CONCLUSIONS: Nascent obesity-induced improvement of cardiac function may be supported by an enhanced coronary reserve occurring via different mechanisms. These mechanisms implicate either the endothelial cells activity or the smooth muscle cells sensitivity depending on the body adiposity of the animals