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

Peter J Gillies,Jerry T Thompson,John P Vanden Heuvel,Leigh A Belcher,Daniel B Hannon,Sujata K Bhatia

doi:10.1194/jlr.m022657

Abstract

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 ω3-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 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 peroxisome proliferator-activated receptor α (PPARα) and PPARβ/γ with minimal effects on PPARγ, liver X receptor, retinoid X receptor, farnesoid X receptor, and retinoid acid receptor γ (RARγ); 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 ω3-PUFA-supplemented individuals. Taken together, these studies indicate regulation of gene expression by EO that is consistent with treating aspects of dyslipidemia and inflammation.

Highlights

Omega-3-PUFAs, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are associated with prevention of various aspects of metabolic syndrome
The dose-dependent regulation of gene expression followed three predominant trends: genes that are increased at the highest dose of EPA-rich oil (EO) (i.e., PLAU, TGF␤1, COL10A); genes that are decreased at the highest dose of EO [i.e., stearoyl CoA desaturase 1 (SCD-1), CYP51A, IDI1, ACAT2]; and genes that are decreased at low doses but increased at high doses of EO (i.e., ILF3, SLC16A3) (Fig. 1)
Animal experiments and human studies have shown that ␻3-PUFAs regulate genes in various tissues, including adipose tissue and peripheral blood mononuclear cells (PBMCs)

Summary

Introduction

Omega-3-PUFAs, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are associated with prevention of various aspects of metabolic syndrome. Other ␻3-PUFAs resulted in a similar gene expression response for a subset of genes involved in lipid metabolism and inflammation. 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 ␻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.

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