Oleic acid is a potent inhibitor of fatty acid and cholesterol synthesis in C6 glioma cells.

Glial cells play a pivotal role in brain fatty acid metabolism and membrane biogenesis. However, the potential regulation of lipogenesis and cholesterologenesis by fatty acids in glial cells has been barely investigated. Here, we show that physiologically relevant concentrations of various saturated, monounsaturated, and polyunsaturated fatty acids significantly reduce [1-(14)C]acetate incorporation into fatty acids and cholesterol in C6 cells. Oleic acid was the most effective at depressing lipogenesis and cholesterologenesis; a decreased label incorporation into cellular palmitic, stearic, and oleic acids was detected, suggesting that an enzymatic step(s) of de novo fatty acid biosynthesis was affected. To clarify this issue, the activities of acetyl-coenzyme A carboxylase (ACC) and FAS were determined with an in situ digitonin-permeabilized cell assay after incubation of C6 cells with fatty acids. ACC activity was strongly reduced ( approximately 80%) by oleic acid, whereas no significant change in FAS activity was observed. Oleic acid also reduced the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). The inhibition of ACC and HMGCR activities is corroborated by the decreases in ACC and HMGCR mRNA abundance and protein levels. The downregulation of ACC and HMGCR activities and expression by oleic acid could contribute to the reduced lipogenesis and cholesterologenesis

Eicosapentaenoic acid modulates the synergistic action of CREB1 and ID/E2A family members in the rat pup brain and mouse embryonic stem cells

The aim of this study was to investigate the molecular mechanism by which eicosapentaenoic acid (EPA) may exert neuroprotective effects through an "EPA-cyclic AMP response element -binding protein (CREB)" signaling pathway. The current study reveals that EPA modulates the exquisite interplay of interaction of CREB1 with the inhibitor of DNA binding (ID) and E2A family members, thereby delivering mechanistic insights into specific neural differentiation program. In this scenario, our work provides evidence for the capability of CREB1 to sequester ID:E2A family members in brain tissues and neural differentiating mouse embryonic stem cells (mESCs) through formation of a [CREB1](2):ID2:E47 tetrameric complex.In essence, the molecular function of CREB1 is to dynamically regulate the location-specific assembly or disassembly of basic-helix-loop-helix (bHLH):HLH protein complexes to mediate the activation of neural/glial target genes. Together, these findings support the one-to-many binding mechanism of CREB1 and indicate that EPA treatment potentiates the integration of CREB dependent signaling with HLH/bHLH transcriptional network, adding specificity to the CREB1-mediated gene regulation during neural/glial differentiation. Our current research on the EPA-CREB axis could reveal new molecular targets for treating neurogenerative disease

Eicosapentaenoic acid modulates the synergistic action of CREB1 and ID/E2A family members in the rat pup brain and mouse embryonic stem cells

International audienceThe aim of this study was to investigate the molecular mechanism by which eicosapentaenoic acid (EPA) may exert neuroprotective effects through an "EPA-cyclic AMP response element-binding protein (CREB)" signaling pathway. The current study reveals that EPA modulates the exquisite interplay of interaction of CREB1 with the inhibitor of DNA binding (ID) and E2A family members, thereby delivering mechanistic insights into specific neural differentiation program. In this scenario, our work provides evidence for the capability of CREB1 to sequester ID:E2A family members in brain tissues and neural differentiating mouse embryonic stem cells (mESCs) through formation of a [CREB1]2:ID2:E47 tetrameric complex.In essence, the molecular function of CREB1 is to dynamically regulate the location-specific assembly or disassembly of basic-helix-loop-helix (bHLH):HLH protein complexes to mediate the activation of neural/glial target genes. Together, these findings support the one-to-many binding mechanism of CREB1 and indicate that EPA treatment potentiates the integration of CREB dependent signaling with HLH/bHLH transcriptional network, adding specificity to the CREB1-mediated gene regulation during neural/glial differentiation. Our current research on the EPA-CREB axis could reveal new molecular targets for treating neurogenerative disease

Micronutriments et Risque Cardiovasculaire : Principaux résultats de l’étude clinique du projet européen Optim’Oils

International audienceLa consommation de micronutriments est associée à une moindre incidence de pathologies cardiovasculaires. Dans ce contexte, le projet européen Optim’Oils (FP6-2005-FOOD 36318) avait pour objectif principal le développement de nouvelles huiles végétales « soft raffinées » plus riches en micronutriments que les huiles raffinées commerciales. Parmi les huiles naturellement « optimisées » en termes de teneur en phytostérols, tocophérols, phénols et co-enzyme Q10, une huile de colza a été évaluée chez l’Homme sain, par comparaison à l’huile de colza raffinée de façon traditionnelle. Il a été montré que la consommation de l’huile de colza « optimisée » comparativement à l’huile de colza classique modulait favorablement la concentration plasmatique en LDL oxydées (-6 %) et en HDL-cholestérol (+ 2 %), deux effets potentiellement impliqués dans la prévention du risque cardiovasculaire

Optimized rapeseed oil enriched with healthy micronutrients: a relevant nutritional approach to prevent cardiovascular diseases. Results of the Optim'Oils randomized intervention trial

Rapeseeds are naturally rich in cardioprotective micronutrients but refining leads to substantial losses or the production of undesirable compounds. The Optim'Oils European project proposed innovative refining conditions to produce an optimized rapeseed oil enriched in micronutrients and low in trans linolenic acid. We aimed to investigate cardioprotective properties of this Optimized oil. In a randomized, double-blind, controlled, cross-over study, 59 healthy normolipidaemic men consumed either Optimized or Standard rapeseed oils (20 g/d) and margarines (22 g/d) for 3 weeks. The Optimized oil reduced the trans FA concentration (p = 0.009) and increased the contents of alpha-tocopherol (p = 0.022) and coenzyme Q10 (p<0.001) in comparison with the Standard oil. Over the 3-week trial, Total-/HDL-cholesterol and LDL-/HDL-cholesterol were increased by 4% (p<0.05) with the Standard oil consumption whereas none of them rose with the Optimized rapeseed oil which increased the HDL-cholesterol and ApoA1 plasma content (+ 2%, NS and +3%, p<0.05 respectively). The effects observed on the plasma HDL-cholesterol levels (p = 0.059), the Total-/HDL-cholesterol ratio (p = 0.092), and on the ApoA1 concentrations (p = 0.060) suggest an improvement of the cholesterol profile with the Optimized rapeseed oil. Finally, the Optimized oil reduced the plasma content of LDLox (-6%, NS), this effect being significantly different from the Standard oil (p = 0.050). In conclusion, reasonable intake of an Optimized rapeseed oil resulting from innovative refining processes and 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. (C) 2013 Elsevier Inc. All rights reserved

Sexual dimorphic evolution of metabolic programming in non-genetic non-alimentary mild metabolic syndrome model in mice depends on feed-back mechanisms integrity for pro-opiomelanocortin-derived endogenous substances

Previously, we showed that our post-natal handling model induces pro-opiomelanocortin-derived (POMC) endogenous systems alterations in male mice at weaning. These alterations last up to adult age, and are at the basis of adult hormonal and metabolic conditions similar to mild metabolic syndrome/type-2 diabetes. Here, we evaluate how sex influences post-natal programming in these metabolic conditions. Subjects are adult control (non-handled) female (NHF) and male (NHM) CD-1 mice; adult post-natal handled female (HF) and male (HM) mice. Handling consists of daily maternal separation (10 min) plus sham injection, from birth to weaning (21 days). In adult handled males (90-days old) we find not only POMC-derived hormones alterations (enhanced basal plasma corticosterone (+91%) and ACTH (+109%)) but also overweight (+5.4%), fasting hyperglycemia (+40%), hypertriglyceridemia (+21%), enhanced brain mRNA expression of hydroxysteroid(11-β)dehydrogenase type-1 (HSD11B1) (+49%), and decreased mRNA-HSD11B2 (−39%). Conversely, uric acid, creatinine, HDL(C), total cholesterol, glucose and insulin incremental area under-the-curve are not affected. In females, post-natal handling does not produce both hormonal and dysmetabolic diabetes-like changes; but handling enhances n3- and n6-poly-unsaturated, and decreases saturated fatty acids content in erythrocyte membrane composition in HF versus NHF. In conclusion, for the first time we show that female sex in mice exerts effective protection against the hypothalamus–pituitary–adrenal homeostasis disruption induced by our post-natal handling model on POMC cleavage products; endocrine disruption is in turn responsible for altered metabolic programming in male mice. The role of sex hormones is still to be elucidated