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

Christoph Handschin, Sherry Chin, Ping Li, Fenfen Liu, Eleftheria Maratos-Flier, Nathan K. LeBrasseur, Zhen Yan, Bruce M. Spiegelman

Research output: Contribution to journalArticle

413 Scopus citations

Abstract

The transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a key integrator of neuromuscular activity in skeletal muscle. Ectopic expression of PGC-1α in muscle results in increased mitochondrial number and function as well as an increase in oxidative, fatigue-resistant muscle fibers. Whole body PGC-1α knock-out mice have a very complex phenotype but do not have a marked skeletal muscle phenotype. We thus analyzed skeletal muscle-specific PGC-1α knock-out mice to identify a specific role for PGC-1α 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-1α 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-1α in maintenance of normal fiber type composition and of muscle fiber integrity following exertion.

Original languageEnglish (US)
Pages (from-to)30014-30021
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number41
DOIs
StatePublished - Oct 12 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1α muscle-specific knock-out animals'. Together they form a unique fingerprint.

  • Cite this