PGC-1 mediates the regulation of metformin in muscle irisin expression and function

Overweight and obesity are rapidly becoming major global health, social, and economic problems. Irisin is a newly termed hormone that is related to metabolic diseases. In the present study, the mechanism underlying the effect of Metformin on promoting irisin release from skeletal muscle was investigated. C57BL/6J-ob/ob was orally administrated with Metformin for 4 weeks. The plasma irisin, insulin, and glucose were detected. Mouse skeletal muscle myoblasts C2C12 cells were treated with Metformin for 24 h. The molecules PGC-1α, FNDC5, AMPK, and ERK mRNA/proteins were quantified by real-time PCR and western blotting in vivo and in vitro. Metformin elevated FNDC5 mRNA/protein expression of skeletal muscle and plasma irisin concentration in ob/ob mice. PGC-1α, p-AMPK and p-ERK protein expression was up-regulated by Metformin in skeletal muscle and C2C12 cells. In addition, the decrease in irisin concentration and protein expression of FNDC5, p-AMPK, and p-ERK induced by siRNA-PGC-1α could not be reversed by Metformin. Our study demonstrates that Metformin stimulates irisin secretion from skeletal muscle into the circulation system of obese mice, and that PGC-1α is a critical regulator in this process.