Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1alpha muscle-specific knock-out animals

J Biol Chem. 2007 Oct 12;282(41):30014-21. doi: 10.1074/jbc.M704817200. Epub 2007 Aug 16.


The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) is a key integrator of neuromuscular activity in skeletal muscle. Ectopic expression of PGC-1alpha in muscle results in increased mitochondrial number and function as well as an increase in oxidative, fatigue-resistant muscle fibers. Whole body PGC-1alpha knock-out mice have a very complex phenotype but do not have a marked skeletal muscle phenotype. We thus analyzed skeletal muscle-specific PGC-1alpha knock-out mice to identify a specific role for PGC-1alpha in skeletal muscle function. These mice exhibit a shift from oxidative type I and IIa toward type IIx and IIb muscle fibers. Moreover, skeletal muscle-specific PGC-1alpha knock-out animals have reduced endurance capacity and exhibit fiber damage and elevated markers of inflammation following treadmill running. Our data demonstrate a critical role for PGC-1alpha in maintenance of normal fiber type composition and of muscle fiber integrity following exertion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Glycolysis
  • Inflammation
  • Mice
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Models, Biological
  • Muscle Fibers, Fast-Twitch / physiology*
  • Muscle Fibers, Slow-Twitch / physiology*
  • Muscle, Skeletal / metabolism*
  • Muscular Diseases / pathology
  • Oxygen / metabolism
  • Physical Conditioning, Animal
  • Transcription Factors / biosynthesis*


  • Transcription Factors
  • peroxisome-proliferator-activated receptor-gamma coactivator-1
  • Oxygen