A role for the transcriptional coactivator PGC-1alpha in muscle refueling.
Wende AR,
Schaeffer PJ,
Parker GJ,
Zechner C,
Han DH,
Chen MM,
Hancock CR,
Lehman JJ,
Huss JM,
McClain DA,
Holloszy JO,
Kelly DP.
Center for Cardiovascular Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) has been identified as an inducible regulator of mitochondrial function. Skeletal muscle PGC-1alpha 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-1alpha gain-of-function and constitutive, generalized, loss-of-function mice. Forced expression of PGC-1alpha increased muscle glucose uptake concomitant with augmentation of glycogen stores, a metabolic response similar to post-exercise recovery. Induction of muscle PGC-1alpha expression prevented muscle glycogen depletion during exercise. Conversely, PGC-1alpha-deficient animals exhibited reduced rates of muscle glycogen repletion post-exercise. PGC-1alpha 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 alpha. These findings identify PGC-1alpha as a critical regulator of skeletal muscle fuel stores.
PMID: 17932032 [PubMed - indexed for MEDLINE]