TY - JOUR
T1 - Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1α muscle-specific knock-out animals
AU - Handschin, Christoph
AU - Chin, Sherry
AU - Li, Ping
AU - Liu, Fenfen
AU - Maratos-Flier, Eleftheria
AU - LeBrasseur, Nathan K.
AU - Yan, Zhen
AU - Spiegelman, Bruce M.
PY - 2007/10/12
Y1 - 2007/10/12
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M704817200
DO - 10.1074/jbc.M704817200
M3 - Article
C2 - 17702743
AN - SCOPUS:35648937073
SN - 0021-9258
VL - 282
SP - 30014
EP - 30021
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 41
ER -