Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 354, Issue 4, Pages 1021-1027Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2007.01.092
Keywords
PGC-l alpha; peroxisome proliferator-activated receptor-gamma coactivator-l alpha; PPAR delta; peroxisome proliferator-activated receptor; skeletal muscle; PGC-l alpha gene promoter
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PGC-1 alpha induces mitochondrial biogenesis in muscle and its activity has been related to insulin sensitization. Here, we report that fibrates induce PGC-1 alpha gene expression in muscle both in vivo and in vitro. However, only activation via PPAR delta but not PPAR alpha underlies this effect. PPAR delta induces PGC-1 alpha gene transcription through a PPAR-response element in the PGC-1 alpha promoter. Moreover, PGC-1 alpha coactivates the PPAR delta-responsiveness of its own gene. A further positive autoregulatory loop of control relies on the induction of PPAR6 expression by PGC-1 alpha. These data point to a distinct value of PPAR6 rather than PPAR alpha agonists in the improvement of oxidative metabolism in muscle. (c) 2007 Elsevier Inc. All rights reserved.
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