Zaigang Yang1, Xu Chen1, Yujuan Chen1, Qian Zhao1. 1. Geriatric Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University Zhengzhou, Henan 450052, China.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: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. CONCLUSION: Our study demonstrates that Metformin stimulates irisin secretion from skeletal muscle into the circulation system of obesemice, and that PGC-1α is a critical regulator in this process.
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