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 EPA or placebo (olive oil). DPA supplementation increased the SPM resolvin D5 n‐3DPA (RvD5 n‐3DPA ) and maresin (MaR)‐1, the DHA vicinal diol 19, 20‐dihydroxy‐DPA and n‐6 PUFA derived 15‐keto‐PG E 2 (15‐keto‐PGE 2 ). 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 and their marked modulation by dietary DPA intake reveals a unique and specific role of n‐3 DPA in human physiology.—Markworth, J. F., Kaur, G., Miller, E.G., Larsen, A. E., Sinclair, A. J., Maddipati, K.R., Cameron‐Smith, D. Divergent shifts in lipid mediator profile following supplementation with n‐3 docosapentaenoic acid and eicosapentaenoic acid. FASEB J. 30, 3714–3725 (2016) www.fasebj.org