Obesity causes several metabolic and chronic diseases, including type 2 diabetes and cardiovascular diseases. Among the omega-3 fatty acids, various health benefits of docosahexaenoic acid (DHA; C22:6n-3) and eicosapentaenoic acid (EPA; C20:5n-3) have been elucidated. This study examined the hypolipidemic effect of DHA and EPA and the epigenetic regulation of DHA and EPA through histone acetyltransferases (HAT) activity. DHA and EPA inhibited the in vitro HAT activity, and non-toxic levels of DHA and EPA significantly attenuated lipid accumulation in 3T3-L1 preadipocytes treated with MDI (IBMX＋dexamethasone＋insulin) and insulin. DHA and EPA regulated the expression of lipogenic, cholesterol-related, or triacylglycerol synthesis-related genes. Indeed, DHA and EPA significantly enhanced PPARα and PPARγ2 in 3T3-L1 preadipocytes treated with MDI and insulin. Although DHA also increased SREBP1α and LXR significantly, EPA significantly attenuated the expression of the SREBP1α and LXR genes. In addition, a lower level of DHA increased AGPAT2 gene expression significantly, which was reduced significantly by the EPA treatment in 3T3-L1 preadipocytes treated with MDI and insulin. These results suggest that the hypolipidemic activity of EPA and DHA is exerted via different gene expression regulation, which is likely to be associated with HAT activity inhibition.

Keywords: DHA, EPA, HAT, 3T3-L1 preadipocytes, AGPAT2