| First Author | Li L | Year | 2011 |
| Journal | Diabetes | Volume | 60 |
| Issue | 1 | Pages | 157-67 |
| PubMed ID | 20929977 | Mgi Jnum | J:170176 |
| Mgi Id | MGI:4944111 | Doi | 10.2337/db10-0331 |
| Citation | Li L, et al. (2011) Mitochondrial biogenesis and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) deacetylation by physical activity: intact adipocytokine signaling is required. Diabetes 60(1):157-67 |
| abstractText | OBJECTIVE Transcriptional peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) plays a key role in mitochondrial biogenesis and energy metabolism and is suggested to be involved in the exercise-induced increase in mitochondrial content. PGC-1alpha activity is regulated by posttranslational modifications, among them acetylation or phosphorylation. Accordingly, the deacetylase SIRT1 and the kinase AMPK increase PGC-1alpha activity. RESEARCH DESIGN AND METHODS We tested whether chronic treadmill exercise or a single exercise session modifies PGC-1alpha activation and mitochondrial biogenesis differentially in obese ob/ob mice with dysregulated adiponectin/leptin-mediated AMPK activation compared with C57BL/6J wild-type mice. RESULTS Exercise training (12 weeks) induced adiponectin and lowered plasma insulin and glucose, suggesting improved insulin sensitivity in wild-type mice. It enhanced mitochondrial biogenesis in red gastrocnemius muscle, as indicated by increased mRNA expression of transcriptional regulators and primary mitochondrial transcripts, increased mtDNA content, and citrate synthase activity. Parallel to this, we observed AMPK activation, PGC-1alpha deacetylation, and SIRT1 induction in trained wild-type mice. Although none of these exercise-induced changes were detected in ob/ob mice, comparable effects on mitochondrial respiration were observed. A single exercise session resulted in comparable changes in wild-type mice. These changes remained detectable 6 h after the exercise session but had disappeared after 24 h. Treatment of C2C12 myoblasts with leptin or adiponectin resulted in increased AMPK phosphorylation and PGC-1alpha deacetylation. CONCLUSIONS Chronic exercise induces mitochondrial biogenesis in wild-type mice, which may require intact AMPK activation by adipocytokines and involve SIRT1-dependent PGC-1alpha deacetylation. Trained ob/ob mice appear to have partially adapted to reduced mitochondrial biogenesis by AMPK/SIRT1/PGC-1alpha-independent mechanisms without mtDNA replication. |
