Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bezafibrate / pharmacology
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Drug Synergism
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Fatty Acids / metabolism
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Female
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Gene Expression Regulation
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Heart / drug effects
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Mice
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Muscle, Skeletal / drug effects
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Muscle, Skeletal / metabolism
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Muscles / metabolism*
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Myocardium / metabolism
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Oxidation-Reduction
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PPAR alpha / physiology*
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PPAR delta / physiology*
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Pyrimidines / pharmacology
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Trans-Activators / biosynthesis*
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Trans-Activators / genetics*
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Transcription Factors
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Transcription, Genetic / drug effects
Substances
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Fatty Acids
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PPAR alpha
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PPAR delta
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Ppargc1a protein, mouse
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Pyrimidines
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Trans-Activators
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Transcription Factors
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pirinixic acid
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Bezafibrate