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There is a high degree of inter-individual variability among people in response to intervention with omega-3 fatty acids (FA), which may partly explain conflicting results on the effectiveness of omega-3 FA for the treatment and prevention of chronic inflammatory diseases. In this study we sought to evaluate whether part of this inter-individual variability in response is related to the regulation of key oxylipin metabolic genes in circulating peripheral blood mononuclear cells (PBMCs).    Methods  Plasma FA and oxylipin profiles from 12 healthy individuals were compared to PBMC gene expression profiles following six weeks of supplementation with fish oil, which delivered 1.9 g/d eicosapentaenoic acid (EPA) and 1.5 g/d docosahexaenoic acid (DHA). Fold changes in gene expression were measured by a quantitative polymerase chain reaction (qPCR).    Results  Healthy individuals supplemented with omega-3 FA had differential responses in prostaglandin-endoperoxide synthase 1 ( PTGS1 ), prostaglandin-endoperoxide synthase 2 ( PTGS2 ), arachidonate 12-lipoxygenase ( ALOX12 ), and interleukin 8 ( IL-8 ) gene expression in isolated PBMCs. In those individuals for whom plasma arachidonic acid (ARA) in the phosphatidylethanolamine (PE) lipid class decreased in response to omega-3 intervention, there was a corresponding decrease in gene expression for  PTGS1  and  ALOX12 . Several oxylipin product/FA precursor ratios (e.g. prostaglandin E 2  (PGE 2 )/ARA for  PTGS1  and 12-hydroxyeicosatetraenoic acid (12-HETE)/ARA for  ALOX12 ) were also associated with fold change in gene expression, suggesting an association between enzyme activity and gene expression. The fold-change in  PTGS1  gene expression was highly positively correlated with  ALOX12  gene expression but not with  PTGS2 , whereas  IL-8  and  PTGS2  were positively correlated.    Conclusions  The regulation of important oxylipin metabolic genes in PBMCs varied with the extent of change in ARA concentrations in the case of  PTGS1  and  ALOX12  regulation. PBMC gene expression changes in response to omega-3 supplementation varied among healthy individuals, and were associated with changes in plasma FA and oxylipin composition to different degrees in different individuals.    Trial Registration  clinicaltrials.gov  NCT01838239

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Changes in PTGS1 and ALOX12 Gene Expression in Peripheral Blood Mononuclear Cells Are Associated with Changes in Arachidonic Acid, Oxylipins, and Oxylipin/Fatty Acid Ratios in Response to Omega-3 Fatty Acid Supplementation