Divergent shifts in lipid mediator profile following supplementation with n-3 docosapentaenoic acid and eicosapentaenoic acid

Abstract

In contrast to the well-characterized effects of specialized proresolving lipid mediators (SPMs) derived fromeicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), little is known about themetabolic fate of the intermediary long-chain (LC) n-3 polyunsaturated fatty acid (PUFA) docosapentaenoic acid (DPA). In this double blind crossover study, shifts in circulating levels of n-3 and n-6 PUFA-derived bioactive lipid mediators were quantified by an unbiased liquid chromatography-Tandem mass spectrometry lipidomic approach. Plasma was obtainedfrom humansubjects before andafter 7 d of supplementationwith pure n-3DPA,n-3 EPAor placebo (olive oil). DPA supplementation increased the SPM resolvin D5n-3DPA (RvD5n-3DPA) and maresin (MaR)-1, the DHA vicinal diol 19,20-dihydroxy-DPA and n-6 PUFA derived 15-keto-PG E2 (15-keto-PGE2). EPA supplementation had no effect on any plasma DPA or DHA derived mediators, but markedly elevated monohydroxy-eicosapentaenoic acids (HEPEs), including the E-series resolvin (RvE) precursor 18-HEPE; effects not observed with DPA supplementation. These data show that dietary n-3 DPA and EPA have highly divergent effects on human lipid mediator profile, with no overlap in PUFA metabolites formed. The recently uncovered biologic activity of n-3 DPA docosanoids andtheirmarkedmodulationby dietaryDPAintake reveals a unique and specific role of n-3DPAinhuman physiology.