Regulation of inflammatory and lipid metabolism genes by eicosapentaenoic acid‐rich oil

Abstract

Omega‐3 polyunsaturated fatty acids (ω3‐PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with prevention of various aspects of metabolic syndrome. In the present studies, the effects of oil rich in EPA on gene expression and activation of nuclear receptors was examined and compared to other ω3‐PUFAs. The EPA‐rich oil (EO) altered the expression of fatty acid metabolism genes in THP‐1 cells including stearoyl CoA desaturase (SCD) and fatty acid desaturase 1 and 2 (FASDS1 and 2). Other ω3‐PUFAs resulted in a similar gene expression response for a subset of genes involved in lipid metabolism and inflammation. In reporter assays, EO activated human PPARα and PPARβ/γ with minimal effects on PPARγ, LXR, RXR, FXR and RARγ; these effects were similar to that observed for purified EPA. When serum from a six week clinical intervention with dietary supplements containing olive oil (control), DHA or two levels of EO were applied to THP‐1 cells, the expression of SCD and FADS2 decreased in the cells treated with serum from the ω3‐PUFA supplemented individuals. Taken together these studies indicate regulation of gene expression by the EPA‐rich oil that is consistent with treating aspects of dyslipidemia and inflammation. (Supported by DuPont Central Research and Development).