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

Academic Article

Abstract

  • 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.
  • Authors

    Published In

    Keywords

  • Animals, Glucose, Glycogen, Glycogen Phosphorylase, Mice, Mice, Transgenic, Mitochondria, Muscle, Muscle Proteins, Muscle, Skeletal, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Phosphorylase Kinase, Trans-Activators, Transcription Factors
  • Digital Object Identifier (doi)

    Pubmed Id

  • 23126598
  • Authorlist

  • Wende AR; Schaeffer PJ; Parker GJ; Zechner C; Han D-H; Chen MM; Hancock CR; Lehman JJ; Huss JM; McClain DA
  • Start Page

  • 36642
  • End Page

  • 36651
  • Volume

  • 282
  • Issue

  • 50