Influence of gender on DHA synthesis: the response of rat liver to low dietary α-linolenic acid evidences higher ω3 ∆4-desaturation index in females.

PURPOSE: The conversion rate of α-linolenic acid (ALA) into docosahexaenoic acid (DHA) is determined by dietary and non-dietary factors. Higher capacity of DHA synthesis has been evidenced in females, indicating that sex factors influence the conversion pathway. To evaluate the extent to which sexual dimorphism of DHA synthesis is subordinated to nutritional handling, we measured the ω3 ∆4-desaturation index in male and female rats receiving adequate or inadequate amounts of ALA. The ω3 ∆4-desaturation index was drawn from the DHA to docosapentaenoic acid (ω3DPA) ratio in liver phospholipids. METHODS: Male and female rats born to ω3-deficient dams were fed a supplemented diet supplying low, inadequate, intermediate, or adequate ALA (5, 20, 100, or 300 mg ALA/100 g diet, respectively). Control rats from both gender received the adequate diet from fetal life. RESULTS: Compared with control, low ALA feeding induced the ω3 ∆4-desaturation index to increase by 38 and 70% in the phosphatidylethanolamine fraction of males and females, respectively, and by 67% in phosphatidylcholine in females only. Supplementations with increased doses of ALA progressively smoothed this gender effect. Moreover, the analysis of our data from a previous study shows that ovariectomy decreased, whereas estradiol treatment increased the ω3 index to values comparable with those of diet-matched males and intact females, respectively. CONCLUSION: Females are more prone than males to increase their index of ω3 ∆4-desaturation, especially in response to low supplies in ALA. Estradiol supports the ω3 index, suggesting that this hormone plays a role in the effect of gender on DHA synthesis.

Long chain-polyunsaturated fatty acids modulate membrane phospholipid composition and protein localization in lipid rafts of neural stem cell cultures.

Rat neural stem cells/neural progenitors (NSC/NP) are generally grown in serum-free medium. In this study, NSC/NP were supplemented with the main long-chain polyunsaturated fatty acids (PUFAs) present in the brain, arachidonic acid (AA), or docosahexaenoic acid (DHA), and were monitored for their growth. Lipid and fatty acid contents of the cells were also determined. Under standard conditions, the cells were characterized by phospholipids displaying a highly saturated profile, and very low levels of PUFAs. When cultured in the presence of PUFAs, the cells easily incorporated them into the phospholipid fraction. We also compared the presence of three membrane proteins in the lipid raft fractions: GFR and connexin 43 contents in the rafts were increased by DHA supplementation, whereas Gbeta subunit content was not significantly modified. The restoration of DHA levels in the phospholipids could profoundly affect protein localization and, consequently, their functionalities.

n-3 PUFA status affects expression of genes involved in neuroenergetics differently in the fronto-parietal cortex compared to the CA1 area of the hippocampus: effect of rest and neuronal activation in the rat.

n-3 Polyunsaturated fatty acids (PUFA) support whole brain energy metabolism but their impact on neuroenergetics in specific brain areas and during neuronal activation is still poorly understood. We tested the effect of feeding rats as control, n-3 PUFA-deficient diet, or docosahexaenoic acid (DHA)-supplemented diet on the expression of key genes in fronto-parietal cortex and hippocampal neuroenergetics before and after neuronal stimulation (activated) by an enriched environment. Compared to control rats, n-3 deficiency specifically repressed GLUT1 gene expression in the fronto-parietal cortex in basal state and also during neuronal activation which specifically stimulated GLUT1. In contrast, in the CA1 area, n-3 deficiency improved the glutamatergic synapse function in both neuronal states (glutamate transporters, Na(+)/K(+) ATPase). DHA supplementation induced overexpression of genes encoding enzymes of the oxidative phosphorylation system and the F1F0 ATP synthase in the CA1 area. We conclude that n-3 deficiency repressed GLUT1 gene expression in the cerebral cortex, while DHA supplementation improved the mitochondrial ATP generation in the CA1 area of the hippocampus.

Long-chain n-3 fatty acid levels in baseline serum phospholipids do not predict later occurrence of depressive episodes: a nested case-control study within a cohort of middle-aged French men and women.

The goal of this study was to seek the relations between baseline n-3 PUFA status and the later occurrence of depressive episodes in a French cohort of middle-aged men and women, the SU.VI.MAX study. A nested case-control study was designed within the cohort: cases with at least two depressive episodes during the 8-year follow-up were paired to non-depressed controls, antidepressant prescriptions being taken as markers of depressive episodes. The fatty acid profiles of baseline serum phospholipids have been determined. Results were analyzed using logistic regression and principal component analysis, taking into account depression history and demographic and lifestyle confounders. There was no consistent association of depression risk with any serum fatty acid, and in particular there was no association of depression risk with the long-chain n-3 PUFA eicosapentaenoic, docosapentaenoic and docosahexaenoic acids. This study does not support the hypothesis of a predictive value of n-3 PUFA status for depression in population settings.