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 (RARβ, RXRβγ and PPARδ), 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 RARβ ( − 14 %) and PPARδ ( − 13 %) along with an increase in RXRβγ (+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.
(Received August 04 2009)
(Revised December 17 2009)
(Accepted December 18 2009)
(Online publication January 27 2010)
Abbreviations: FAME, fatty acid methyl esters; HFD, high-fat diet; NR, nuclear receptors; PE, phosphatidylethanolamine; RA, retinoic acid; RAR, RA receptor; RXR, retinoid X receptor