A Role for the Transcriptional Coactivator PGC-1α in Muscle Refueling

• Published in: The Journal of biological chemistry 2007-12, Vol.282 (50), p.36642-36651
• Main Authors: Wende, Adam R., Schaeffer, Paul J., Parker, Glendon J., Zechner, Christoph, Han, Dong-Ho, Chen, May M., Hancock, Chad R., Lehman, John J., Huss, Janice M., McClain, Donald A., Holloszy, John O., Kelly, Daniel P.
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M707006200

The transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) has been identified as an inducible regulator of mitochondrial function. Skeletal muscle PGC-1α expression is induced post-exercise. Therefore, we sought to determine its role in the regulation of muscle fuel metabolism. Studies were performed using conditional, muscle-specific, PGC-1α gain-of-function and constitutive, generalized, loss-of-function mice. Forced expression of PGC-1α increased muscle glucose uptake concomitant with augmentation of glycogen stores, a metabolic response similar to post-exercise recovery. Induction of muscle PGC-1α expression prevented muscle glycogen depletion during exercise. Conversely, PGC-1α-deficient animals exhibited reduced rates of muscle glycogen repletion post-exercise. PGC-1α was shown to increase muscle glycogen stores via several mechanisms including stimulation of glucose import, suppression of glycolytic flux, and by down-regulation of the expression of glycogen phosphorylase and its activating kinase, phosphorylase kinase α. These findings identify PGC-1α as a critical regulator of skeletal muscle fuel stores.