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

The activity of AMP-activated protein kinase alpha (AMPK alpha) 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 free fatty add (FFA) participates in muscular impairment. The purpose of the present study was to explore whether FFA damages myogenesis through the AMPK alpha-histone deacetylase 4 (HDAC4)-microRNA 206 (miR-206) pathway. The results showed that 1 mM FFA produced lipid accumulation, significantly impaired the insulin signaling pathway, and decreased the myogenic differentiation of C2C12 myoblast cells. FFA reduced the LKB1-AMPK alpha pathway, and the activation of AMPK alpha rescued the myogenic impairment caused by FFA (P < 0.05). AMPK alpha promoted myogenesis by regulating the expression of miR-206 through HDAC4 (P < 0.05) and affected the cell cycle and cell proliferation to promote myogenesis by regulating miR-206 and miR-206's target cyclin D1 gene. In addition, AICAR (5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside) and HDAC4 small interfering RNA (siRNA) promoted myogenic differentiation compared with the FFA group; however, this positive effect was significantly downregulated after transfection with the miR-206 inhibitor. In summary, AMPK alpha plays positive roles in myogenic differentiation and myogenesis, and FFA decreased myogenic differentiation and myotube formation through the AMPK alpha-HDAC4-miR-206 pathway.

Automated summary

This study found that FFA reduces myogenic differentiation and myotube formation through the AMPK alpha-HDAC4-miR-206 pathway.