Abstract
Exogenous administration of eicosapentaenoic acid (EPA) improves insulin sensitivity, 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-induced activities including tyrosine phosphorylation of insulin receptor substrate-1, insulin receptor substrate-1-associated phosphatidylinositol 3-kinase, and its downstream target Akt kinase activity as well as down-regulation of gluconeogenesis. In contrast, EPA decreased mitogen-activated protein kinase activity and inhibited cell proliferation. These findings raise the possibility that EPA up-regulates metabolic action of insulin and inhibits cell growth in humans.
Highlights
Exogenous administration of eicosapentaenoic acid (EPA) improves insulin sensitivity, but its precise mechanism remains unknown
We demonstrated for the first time that EPA treatment for 24 h caused stimulation of both the basal and insulin-induced insulin receptor substrate-1 (IRS-1)-PI3K pathway in HepG2 cells as well as reduction of the amount of PEPCK mRNA expression in H4-II-E cells
It is of great interest that tyrosine phosphorylation of IRS-1 is specific for EPA, since other fatty acids cannot induce tyrosine phosphorylation of IRS-1
Summary
Exogenous administration of eicosapentaenoic acid (EPA) improves insulin sensitivity, but its precise mechanism remains unknown. We show that EPA stimulates the intracellular insulin signaling pathway in hepatoma cells. EPA decreased mitogenactivated protein kinase activity and inhibited cell proliferation. These findings raise the possibility that EPA up-regulates metabolic action of insulin and inhibits cell growth in humans. Accumulating evidence in animal and human studies indicates that administration of n-3 PUFAs improves insulin sensitivity [1,2,3,4]. The present study is aimed at clarifying whether EPA directly affects insulin signaling in target tissues via the other novel mechanism ameliorating insulin sensitivity as well as cell proliferation
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