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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-1370

Handschin, C; Chin, S; Li, P; Liu, F; Maratos-Flier, E; Lebrasseur, N K; Yan, Z; Spiegelman, B M (2007). Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1alpha muscle-specific knock-out animals. Journal of Biological Chemistry, 282(41):30014-30021.

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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.


259 citations in Web of Science®
277 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
Date:12 October 2007
Deposited On:11 Feb 2008 12:22
Last Modified:05 Apr 2016 12:18
Publisher:American Society for Biochemistry and Molecular Biology
Publisher DOI:10.1074/jbc.M704817200
PubMed ID:17702743

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