APOE Genotype Modifies the Plasma Oxylipin Response to Omega-3 Polyunsaturated Fatty Acid Supplementation in Healthy Individuals

The omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic (DHA), mediate inflammation in large part by affecting pro-inflammatory anti-inflammatory/pro-resolving oxylipin concentrations. Common gene variants are thought to underlie the inter-individual variation levels response n-3 PUFA supplementation, which turn is likely contribute overall heterogeneity intervention. Given its known role as a modulator of physiological EPA DHA, here we explore, for first time, differential plasma hydroxy-, epoxy- dihydroxy-arachidonic acid, DHA oxylipins according apolipoprotein E ( APOE ) genotype using samples from dose-response parallel design RCT. Healthy participants were given doses EPA+DHA equivalent intakes 1, 2, 4 portions oily fish per week 12 months. There was no difference EPA, or ARA between wildtype APOE3/E3 APOE4 carrier groups after 3 months supplementation. At months, hydroxy EPAs (HEPEs) hydroxy-DHAs (HDHAs) higher carriers, with most evident at highest intake. A significant * dose effect observed CYP-ω hydroxylase products 19-HEPE p = 0.027) 20-HEPE 0.011). 8-HEPE, which, along several other oxylipins, an activator peroxisome proliferator activated receptors (PPARs), showed fold change carriers (14-fold) compared (4-fold) 0.014). Low basal (EPA < 0.85% total acids) associated greater 5-HEPE, 9-HEPE, 11-HEPE, high > 1.22% acids). In conclusion, modulated increased intake, presenting greatest increases following supplementation