Article

PPARdelta, but not PPARalpha, activates PGC-1alpha gene transcription in muscle.

Department of Biochemistry and Molecular Biology, University of Barcelona, 08028 Barcelona, Spain.
Biochemical and Biophysical Research Communications (impact factor: 2.48). 04/2007; 354(4):1021-7. DOI:10.1016/j.bbrc.2007.01.092 pp.1021-7
Source: PubMed

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.

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Keywords

data point
 
fibrates induce PGC-1alpha gene expression
 
insulin sensitization
 
oxidative metabolism
 
PGC-1alpha induces mitochondrial biogenesis
 
positive autoregulatory loop
 
PPARalpha agonists
 
PPARdelta
 
PPARdelta expression
 
PPARdelta induces PGC-1alpha gene transcription
 
PPARdelta-responsiveness
 
vitro