PPARdelta, but not PPARalpha, activates PGC-1alpha gene transcription in muscle.
PGC-1alpha induces mitochondrial biogenesis in muscle and its activity has been related to insulin sensitization. Here, we report that fibrates induce PGC-1alpha gene expression in muscle both in vivo and in vitro. However, only activation via PPARdelta but not PPARalpha underlies this effect. PPARdelta induces PGC-1alpha gene transcription through a PPAR-response element in the PGC-1alpha promoter. Moreover, PGC-1alpha coactivates the PPARdelta-responsiveness of its own gene. A further positive autoregulatory loop of control relies on the induction of PPARdelta expression by PGC-1alpha. These data point to a distinct value of PPARdelta rather than PPARalpha agonists in the improvement of oxidative metabolism in muscle.
Hondares
Elayne
E
Department of Biochemistry and Molecular Biology, University of Barcelona, 08028 Barcelona, Spain.
Pineda-Torra
Inés
I
Iglesias
Roser
R
Staels
Bart
B
Villarroya
Francesc
F
Giralt
Marta
M
D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology; D004357:Drug Synergism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006321:Heart / Q000187:drug effects; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000502:physiology*; D047494:PPAR delta / Q000502:physiology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011743:Pyrimidines / Q000494:pharmacology; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics*; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects
D005227:Fatty Acids; D047493:PPAR alpha; D047494:PPAR delta; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D011743:Pyrimidines; D015534:Trans-Activators; D014157:Transcription Factors; C006253:pirinixic acid; D001629:Bezafibrate