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

Omega-3-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 with other omega 3-PUFAs. The EPA-rich oil (EO) altered the expression of FA metabolism genes in THP-1 cells, including stearoyl CoA desaturase (SCD) and FA desaturase-1 and -2 (FASDS1 and -2). Other omega 3-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 peroxisome proliferator-activated receptor alpha (PPAR alpha) and PPAR beta/gamma with minimal effects on PPAR gamma, liver X receptor, retinoid X receptor, farnesoid X receptor, and retinoid acid receptor gamma (RAR gamma); these effects were similar to that observed for purified EPA. When serum from a 6 week clinical intervention with dietary supplements containing olive oil (control), DHA, or two levels of EPA were applied to THP-1 cells, the expression of SCD and FADS2 decreased in the cells treated with serum from the omega 3-PUFA-supplemented individuals. Taken together, these studies indicate regulation of gene expression by EO that is consistent with treating aspects of dyslipidemia and inflammation.-Gillies, P. J., S. K. Bhatia, L. A. Belcher, D. B. Hannon, J. T. Thompson, and J. P. Vanden Heuvel. Regulation of inflammatory and lipid metabolism genes by eicosapentaenoic acid-rich oil. J. Lipid Res. 2012. 53: 1679-1689.