title: PGC-1 mediates the regulation of metformin in muscle irisin expression and function.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Geriatric Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University Zhengzhou, Henan 450052, China.
authors.forename: Zaigang
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Geriatric Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University Zhengzhou, Henan 450052, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Geriatric Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University Zhengzhou, Henan 450052, China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Geriatric Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University Zhengzhou, Henan 450052, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
keywords: FNDC5; Metformin; diabetes; obesity mice