Changes in <i>PTGS1</i> and <i>ALOX12</i> 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

<div><p>Introduction</p><p>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).</p><p>Methods</p><p>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).</p><p>Results</p><p>Healthy individuals supplemented with omega-3 FA had differential responses in prostaglandin-endoperoxide synthase 1 (<i>PTGS1</i>), prostaglandin-endoperoxide synthase 2 (<i>PTGS2</i>), arachidonate 12-lipoxygenase (<i>ALOX12</i>), and interleukin 8 (<i>IL-8</i>) 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 <i>PTGS1</i> and <i>ALOX12</i>. Several oxylipin product/FA precursor ratios (e.g. prostaglandin E₂ (PGE₂)/ARA for <i>PTGS1</i> and 12-hydroxyeicosatetraenoic acid (12-HETE)/ARA for <i>ALOX12</i>) were also associated with fold change in gene expression, suggesting an association between enzyme activity and gene expression. The fold-change in <i>PTGS1</i> gene expression was highly positively correlated with <i>ALOX12</i> gene expression but not with <i>PTGS2</i>, whereas <i>IL-8</i> and <i>PTGS2</i> were positively correlated.</p><p>Conclusions</p><p>The regulation of important oxylipin metabolic genes in PBMCs varied with the extent of change in ARA concentrations in the case of <i>PTGS1</i> and <i>ALOX12</i> 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.</p><p>Trial Registration</p><p>clinicaltrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01838239?term=NCT01838239&rank=1" target="_blank">NCT01838239</a></p>