Dual action of eicosapentaenoic acid in hepatoma cells - Up-regulation of metabolic action of insulin and inhibition of cell proliferation

Exogenous administration of eicosapentaenoic acid (EPA) improves insulin se nsitivity, but its precise mechanism remains unknown. Here we show that EPA stimulates the intracellular insulin signaling pathway in hepatoma cells. Exposure of these cells to EPA caused up-regulation of several insulin-indu ced activities including tyrosine phosphorylation of insulin receptor subst rate-1, insulin receptor substrate-l-associated phosphatidylinositol 3-kina se, and its downstream target Akt kinase activity as well as down-regulatio n of gluconeogenesis. In contrast, EPA decreased mitogenactivated protein k inase activity and inhibited cell proliferation. These findings raise the p ossibility that EPA up-regulates metabolic action of insulin and inhibits c ell growth in humans.