PGC1alpha expression is controlled in skeletal muscles by PPARbeta, whose ablation results in fiber-type switching, obesity, and type 2 diabetes.
Mice in which peroxisome proliferator-activated receptor beta (PPARbeta) is selectively ablated in skeletal muscle myocytes were generated to elucidate the role played by PPARbeta signaling in these myocytes. These somatic mutant mice exhibited a muscle fiber-type switching toward lower oxidative capacity that preceded the development of obesity and diabetes, thus demonstrating that PPARbeta is instrumental in myocytes to the maintenance of oxidative fibers and that fiber-type switching is likely to be the cause and not the consequence of these metabolic disorders. We also show that PPARbeta stimulates in myocytes the expression of PGC1alpha, a coactivator of various transcription factors, known to play an important role in slow muscle fiber formation. Moreover, as the PGC1alpha promoter contains a PPAR response element, the effect of PPARbeta on the formation and/or maintenance of slow muscle fibers can be ascribed, at least in part, to a stimulation of PGC1alpha expression at the transcriptional level.
Schuler
Michael
M
IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), Department of Physiological Genetics, Illkirch, F-67400 France.
Ali
Faisal
F
Chambon
Céline
C
Duteil
Delphine
D
Bornert
Jean-Marc
JM
Tardivel
Aubry
A
Desvergne
Béatrice
B
Wahli
Walter
W
Chambon
Pierre
P
Metzger
Daniel
D
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism; D017353:Gene Deletion; D006360:Heat-Shock Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D032342:Muscle Cells / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000209:etiology*; D048068:PPAR-beta / Q000235:genetics / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors / Q000378:metabolism*
D006360:Heat-Shock Proteins; D048068:PPAR-beta; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors