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
| Autor: | Jun Yang, Angela M. Zivkovic, Shizuo G. Kamita, Malin L. Nording, Katrin Georgi, Ronald J. Hogg, Christine Hegedus Karbowski, Claire C. Berthelot, Robert H. Weiss, Romina Sacchi, Bruce D. Hammock, J. Bruce German |
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| Přispěvatelé: | Norata, Giuseppe Danilo |
| Rok vydání: | 2015 |
| Předmět: |
Enzymologic
General Science & Technology Mononuclear PTGS1 Prostaglandin lcsh:Medicine Biology Arachidonate 12-Lipoxygenase Peripheral blood mononuclear cell Gene Expression Regulation Enzymologic Microbiology in the medical area Body Mass Index chemistry.chemical_compound Clinical Research Complementary and Integrative Health parasitic diseases Blood plasma Fatty Acids Omega-3 Mikrobiologi inom det medicinska området Genetics Leukocytes 2.1 Biological and endogenous factors Humans Oxylipins Aetiology lcsh:Science Medicinsk genetik Nutrition chemistry.chemical_classification Omega-3 Multidisciplinary Arachidonic Acid Prevention lcsh:R Fatty Acids Fatty acid Oxylipin 3. Good health ALOX12 Biochemistry chemistry Gene Expression Regulation Dietary Supplements Leukocytes Mononuclear Cyclooxygenase 1 Arachidonic acid lcsh:Q Medical Genetics Research Article |
| Zdroj: | PloS one, vol 10, iss 12 PLoS ONE PLoS ONE, Vol 10, Iss 12, p e0144996 (2015) |
| Popis: | Introduction 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 E2 (PGE2)/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 |
| Databáze: | OpenAIRE |
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