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We investigated the impact of increased alpha-linolenic acid (ALA) dietary levels on its plasma bioavailability and its bioconversion in n -3 long chain poly unsaturated fatty acids during a 60-d kinetics and the oxidative stress potentially associated. Rats were submitted to a normolipidic diet providing 0, 3, 10 and 24% ALA of dietary lipids for 0, 15, 30 and 60 days. The lipid peroxidation and oxidative stress (nitric oxide (NO) contents and catalase (CAT), superoxide dismutase (SOD), gluthation peroxidase (GPx) activities) were studied in the liver and plasma. When the diet was deprived in n -3 PUFAs, ALA, (eicosanoic acid) EPA and docosahexaenoic acid (DHA) levels decreased in all lipid fractions of plasma and in red blood cell (RBC) lipids. The addition of ALA in the diet linearly improves its bioavailability and its bioconversion in EPA ( R ²=0.98). By providing 10 to 24% ALA in dietary lipids (LA/ALA, 1·6 and 5·5 respectively), ALA and EPA were more broadly packaged in all lipid fractions (triglyceride (TAG), cholesterol ester (CE) and free fatty acids (FFA)) of plasma from 15 to 30 days timeframe. Only 3% ALA was sufficient to promote the maximal bioconversion of ALA in DHA in phospholipid (PL) and TAG fractions. Additionally, the improvement of ALA bioconversion in EPA and DHA did not impact the oxidative stress markers and limiting lipid peroxidation. To conclude, this study demonstrated that in rat, 10% ALA in the lipid diet for 15-30 days promotes its bioavailability and its bioconversion and allowed the greatest levels in plasma and RBCs.

n-3 Long-chain PUFA (n-3 LC-PUFA), particularly EPA and DHA, play a key role in the maintenance of brain functions such as learning and memory that are impaired during ageing. Ageing is also associated with changes in the DHA content of brain membranes that could contribute to memory impairment. Limited studies have investigated the effects of ageing and n-3 LC-PUFA supplementation on both blood and brain fatty acid compositions. Therefore, we assessed the relationship between fatty acid contents in plasma and erythrocyte membranes and those in the hippocampus, striatum and cerebral cortex during ageing, and after a 5-month period of EPA/DHA supplementation in rats. In the blood, ageing was associated with an increase in plasma DHA content, whereas the DHA content remained stable in erythrocyte membranes. In the brain, ageing was associated with a decrease in DHA content, which was both region-specific and phospholipid class-specific. In EPA/DHA-supplemented aged rats, DHA contents were increased both in the blood and brain compared with the control rats. The present results demonstrated that n-3 LC-PUFA level in the plasma was not an accurate biomarker of brain DHA status during ageing. Moreover, we highlighted a positive relationship between the DHA levels in erythrocyte phosphatidylethanolamine (PE) and those in the hippocampus and prefrontal cortex in EPA/DHA-supplemented aged rats. Within the framework of preventive dietary supplementation to delay brain ageing, these results suggest the possibility of using erythrocyte PE DHA content as a reliable biomarker of DHA status in specific brain regions.

Numerous studies have reported an association between cognitive impairment in old age and nutritional factors, including dietary fat. Retinoic acid (RA) plays a central role in the maintenance of cognitive processes via its nuclear receptors (NR), retinoic acid receptor (RAR) and retinoid X receptor (RXR), and the control of target genes, e.g. the synaptic plasticity markers GAP-43/neuromodulin and RC3/neurogranin. Given the relationship between RA and the fatty acid signalling pathways mediated by their respective NR (RAR/RXR and PPAR), we investigated the effect of a high-fat diet (HFD) on (1) PUFA status in the plasma and brain, and (2) the expression of RA and fatty acid NR (RARbeta, RXRbetagamma and PPARdelta), and synaptic plasticity genes (GAP-43 and RC3), in young male Wistar rats. In the striatum of rats given a HFD for 8 weeks, real-time PCR (RT-PCR) revealed a decrease in mRNA levels of RARbeta ( - 14 %) and PPARdelta ( - 13 %) along with an increase in RXRbetagamma (+52 %). Concomitantly, RT-PCR and Western blot analysis revealed (1) a clear reduction in striatal mRNA and protein levels of RC3 ( - 24 and - 26 %, respectively) and GAP-43 ( - 10 and - 42 %, respectively), which was confirmed by in situ hybridisation, and (2) decreased hippocampal RC3 and GAP-43 protein levels (approximately 25 %). Additionally, HFD rats exhibited a significant decrease in plasma ( - 59 %) and brain ( - 6 %) n-3 PUFA content, mainly due to the loss of DHA. These results suggest that dietary fat induces neurobiological alterations by modulating the brain RA signalling pathway and n-3 PUFA content, which have been previously correlated with cognitive impairment.