PPARδ, but not PPARα, activates PGC-1α gene transcription in muscle

PGC-1α induces mitochondrial biogenesis in muscle and its activity has been related to insulin sensitization. Here, we report that fibrates induce PGC-1α gene expression in muscle both in vivo and in vitro. However, only activation via PPARδ but not PPARα underlies this effect. PPARδ induces PGC-1α gene transcription through a PPAR-response element in the PGC-1α promoter. Moreover, PGC-1α coactivates the PPARδ-responsiveness of its own gene. A further positive autoregulatory loop of control relies on the induction of PPARδ expression by PGC-1α. These data point to a distinct value of PPARδ rather than PPARα agonists in the improvement of oxidative metabolism in muscle.