Free Fatty Acid Impairs Myogenic Differentiation through the AMPKα-MicroRNA 206 Pathway

Abstract

The activity of AMPKα is reduced in type-2 diabetes, and type-2 diabetes is associated with muscular atrophy. To date, there is little known about the mechanism by which FFA participates in muscular impairment. The purpose of the present study was to explore whether FFA damages myogenesis through AMPKα-HDAC4-miR-206 pathway. The results showed that 1mM FFA produced lipid accumulation, significantly impaired insulin signaling pathway and decreased myogenic differentiation of C2C12 myoblast cells. FFA reduced LKB1-AMPKα pathway; activation of AMPKα rescued the myogenic impairment caused by FFA (P < 0.05). AMPKα promoted myogenesis by regulating the expression of miR-206 through HDAC4 (P < 0.05); AMPKα affected cell cycle and cell proliferation to promote myogenesis by regulating miR-206 and miR-206’s target gene - cyclin D1. In addition, AICAR and HDAC4 siRNA promoted myogenic differentiation compared with FFA group; however, this positive effect was significantly down-regulated after transfection of miR-206 inhibitor. In summary, AMPKα plays positive roles in myogenic differentiation and myogenesis, and FFA decreased myogenic differentiation and myotubes formation through AMPKα-HDAC4-miR-206 pathway.