Adiponectin increases skeletal muscle mitochondrial biogenesis by suppressing mitogen-activated protein kinase phosphatase-1

Diabetes. 2012 Jun;61(6):1463-70. doi: 10.2337/db11-1475. Epub 2012 Mar 13.

Abstract

Adiponectin enhances mitochondrial biogenesis and oxidative metabolism in skeletal muscle. This study aimed to investigate the underlying mechanisms through which adiponectin induces mitochondrial biogenesis in skeletal muscle. Mitochondrial contents, expression, and activation status of p38 mitogen-activated protein kinase (MAPK) and PPARγ coactivator 1α (PGC-1α) were compared between skeletal muscle samples from adiponectin gene knockout, adiponectin-reconstituted, and control mice. Adenovirus-mediated adiponectin and MAPK phosphatase-1 (MKP1) overexpression were used to verify the relationship of MKP1 and PGC-1α in adiponectin-enhanced mitochondrial biogenesis using cultured C2C12 myotubes and PGC-1α knockout mice. An inhibitory effect of adiponectin on MKP1 gene expression was observed in mouse skeletal muscle and cultured C2C12 myotubes. Overexpression of MKP1 attenuated adiponectin-enhanced mitochondrial biogenesis, with significantly decreased PGC-1α expression and p38 MAPK phosphorylation. Although in vivo adiponectin overexpression reduced MKP1 protein levels, the stimulative effects of adiponectin on mitochondrial biogenesis vanished in skeletal muscle of PGC-1α knockout mice. Therefore, our study indicates that adiponectin enhances p38 MAPK/PGC-1α signaling and mitochondrial biogenesis in skeletal muscle by suppressing MKP1 expression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / genetics
  • Adiponectin / metabolism*
  • Animals
  • Cells, Cultured
  • Gene Expression
  • Mice
  • Mice, Knockout
  • Mitochondria, Muscle / metabolism*
  • Mitogen-Activated Protein Kinase Phosphatases / genetics
  • Mitogen-Activated Protein Kinase Phosphatases / metabolism*
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / metabolism*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Signal Transduction / physiology
  • Trans-Activators / metabolism
  • Transcription Factors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Adiponectin
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Trans-Activators
  • Transcription Factors
  • p38 Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Phosphatases