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

387 Citations (Scopus)

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
Externally publishedYes

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Skeletal Muscle Fibers
Muscular Diseases
Muscle
Animals
Skeletal Muscle
Muscles
Fibers
Knockout Mice
Phenotype
Muscle Fatigue
Peroxisome Proliferator-Activated Receptors
Running
Maintenance
Exercise equipment
Inflammation
Durability
Fatigue of materials
Chemical analysis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1α muscle-specific knock-out animals. / Handschin, Christoph; Chin, Sherry; Li, Ping; Liu, Fenfen; Maratos-Flier, Eleftheria; LeBrasseur, Nathan K; Yan, Zhen; Spiegelman, Bruce M.

In: Journal of Biological Chemistry, Vol. 282, No. 41, 12.10.2007, p. 30014-30021.

Research output: Contribution to journalArticle

Handschin, Christoph ; Chin, Sherry ; Li, Ping ; Liu, Fenfen ; Maratos-Flier, Eleftheria ; LeBrasseur, Nathan K ; Yan, Zhen ; Spiegelman, Bruce M. / Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1α muscle-specific knock-out animals. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 41. pp. 30014-30021.
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