A role for the transcriptional coactivator PGC-1α in muscle refueling

Adam R. Wende, Paul J. Schaeffer, Glendon J. Parker, Christoph Zechner, Dong Ho Han, May M. Chen, Chad R. Hancock, John J. Lehman, Janice M. Huss, Donald A. McClain, John O. Holloszy, Daniel P. Kelly

Research output: Contribution to journalArticle

179 Scopus citations

Abstract

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 postexercise 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.

Original languageEnglish (US)
Pages (from-to)36642-36651
Number of pages10
JournalJournal of Biological Chemistry
Volume282
Issue number50
DOIs
StatePublished - Dec 14 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Wende, A. R., Schaeffer, P. J., Parker, G. J., Zechner, C., Han, D. H., Chen, M. M., Hancock, C. R., Lehman, J. J., Huss, J. M., McClain, D. A., Holloszy, J. O., & Kelly, D. P. (2007). A role for the transcriptional coactivator PGC-1α in muscle refueling. Journal of Biological Chemistry, 282(50), 36642-36651. https://doi.org/10.1074/jbc.M707006200