Skeletal Muscle Fiber-type Switching, Exercise Intolerance, and Myopathy in PGC-1α Muscle-specific Knock-out Animals
LeBrasseur, Nathan K.
Spiegelman, Bruce M.
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CitationHandschin, Christoph, Sherry Chin, Ping Li, Fenfen Liu, Eleftheria Maratos-Flier, Nathan K. LeBrasseur, Zhen Yan, and Bruce M. Spiegelman. 2007. “Skeletal Muscle Fiber-Type Switching, Exercise Intolerance, and Myopathy in PGC-1α Muscle-Specific Knock-out Animals.” Journal of Biological Chemistry 282 (41): 30014–21. doi:10.1074/jbc.M704817200.
AbstractThe transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) is a key integrator of neuromuscular activity in skeletal muscle. Ectopic expression of PGC-1 alpha in muscle results in increased mitochondrial number and function as well as an increase in oxidative, fatigue-resistant muscle fibers. Whole body PGC-1 alpha knock-out mice have a very complex phenotype but do not have a marked skeletal muscle phenotype. We thus analyzed skeletal muscle-specific PGC-1 alpha knock-out mice to identify a specific role for PGC-1 alpha 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-1 alpha 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-1 alpha in maintenance of normal fiber type composition and of muscle fiber integrity following exertion.
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