A diet rich in omega-3 fatty acids enhances expression of soluble epoxide hydrolase in murine brain

Several studies suggest that intake of omega-3 polyunsaturated fatty acids (n3-PUFA) beneficially influences cognitive function. However, effects on the adult brain are not clear. Little is known about the impact of dietary intervention on the fatty acid profile in adult brain, the modulation in the expression of enzymes involved in fatty acid biosynthesis and metabolism as well as changes in resulting oxylipins. These questions were addressed in the present study in two independent n3-PUFA feeding experiments in mice. Supplementation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA, 1% each in the diet) for 30 days to adult NMRI and C57BL/6 mice led to a distinct shift in the brain PUFA pattern. While n3-PUFAs EPA, n3 docosapentaenoic acid and DHA were elevated, many n6-PUFAs were significantly decreased (except, e.g. C20:3 n6 which was increased). This shift in PUFAs was accompanied by immense differences in concentrations of oxidative metabolites derived from enzymatic conversion of PUFAs, esp. arachidonic acid whose products were uniformly decreased, and a modulation in the activity and expression pattern of delta-5 and delta-6 desaturases. In both mouse strains a remarkable increase in the soluble epoxide hydrolase (sEH) activity (decreased epoxy-FA concentrations and epoxy-FA to dihydroxy-FA-ratios) as well as sEH expression was observed. Taking the high biological activity of epoxy-FA, e.g. on blood flow and nociceptive signaling into account, this finding might be of relevance for the effects of n3-PUFAs in neurodegenerative diseases. On any account, our study suggests a new distinct regulation of brain PUFA and oxylipin pattern by supplementation of n3-PUFAs to adult rodents.