Adiponectin Increases Skeletal Muscle Mitochondrial Biogenesis by Suppressing Mitogen-Activated Protein Kinase Phosphatase-1

• Published in: Diabetes (New York, N.Y.) Vol. 61; no. 6; pp. 1463 - 1470
• Main Authors: LIPING QIAO, KINNEY, Brice, HYUNG SUN YOO, LEE, Bonggi, SCHAACK, Jerome, JIANHUA SHAO
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.06.2012
• Subjects: Adenoviruses; Adiponectin - genetics; Adiponectin - metabolism; Animals; Biological and medical sciences; Biosynthesis; Cells, Cultured; Diabetes; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fundamental and applied biological sciences. Psychology; Gene Expression; Health aspects; Homeostasis; Insulin resistance; Kinases; Laboratory animals; Medical sciences; Metabolism; Metabolites; Mice; Mice, Knockout; Mitochondria, Muscle - metabolism; Mitochondrial biogenesis; Mitogen-Activated Protein Kinase Phosphatases - genetics; Mitogen-Activated Protein Kinase Phosphatases - metabolism; Muscle Fibers, Skeletal - metabolism; Muscle, Skeletal - metabolism; Muscles; Musculoskeletal system; Obesity; Obesity Studies; p38 Mitogen-Activated Protein Kinases - metabolism; Penicillin; Peptide hormones; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Phosphatase; Phosphorylation; Physiological aspects; Proteins; Signal Transduction - physiology; Skeletal muscle; Striated muscle. Tendons; Trans-Activators - metabolism; Transcription Factors; Vertebrates: osteoarticular system, musculoskeletal system; United States; Endocrinopathy; Mitochondria; Enzyme; Transferases; Diabetes mellitus; Mitogen-activated protein kinase; Adipokine; Striated muscle; Adiponectin
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db11-1475

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.