RESUMO
Insulin resistance is defined as a failure to trigger the activation of the PI3K-AKT pathway by normal levels of insulin; therefore, it is well linked to metabolic disorders. Although multiple mechanisms contribute to insulin resistance, one major cause is elevated concentrations of plasma free fatty acids, which are known to suppress insulin signaling. However, the underlying mechanism is still elusive. Here, we found that palmitic acid increased the expression of two miRNAs, miR-3180-3p and miR-4632-5p, in HepG2 cells. Transfection of HepG2 cells with miR-3180-3p or miR-4632-5p reduced insulin-induced activation of the PI3K-AKT pathway. Moreover, palmitic acid or two miRNAs inhibited insulin-induced phosphorylation of Tyr612 on IRS-1 without affecting insulin receptor activation. Therefore, two miRNAs are suggested to be involved in palmitic acid-induced insulin resistance through suppression of insulin-induced IRS-1 phosphorylation. Identification of miR-3180-3p and miR-4632-5p targets could provide valuable information for the development of therapeutic drugs for type 2 diabetes.
Assuntos
Resistência à Insulina/genética , MicroRNAs/genética , Ácido Palmítico/efeitos adversos , Regulação para Cima , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Modelos Biológicos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
We investigated the effect of a water-soluble extract from Grifola frondosa, the maitake mushroom, on lipid droplets in brown adipocyte tissue (BAT) cells. This water-soluble extract inhibits the conversion of pre white adipocyte tissue (WAT) cells but does not inhibit that of pre BAT cells. It reduces the amount of accumulated triglycerides (TG) in BAT cells. The glycerol-3-phosphate dehydrogenase (GPDH) activities of BAT cells decreased, but the expression of uncoupling protein 1 (UCP1) levels increased. These results suggest that maitake extract inhibits TG accumulation-related energy metabolism.