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 SupplementationReportar como inadecuado




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 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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



Autor: Claire C. Berthelot, Shizuo George Kamita, Romina Sacchi, Jun Yang, Malin L. Nording, Katrin Georgi, Christine Hegedus Karbowski,

Fuente: http://plos.srce.hr/



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