Overexpression of PPARδ in skeletal muscle from transgenic mice induces expression of genes related to fatty
PF-4981517 transport and oxidation such as CPT1β[29] and [30]. Cardiac-restricted knock-out of PPARδ showed that PPARδ is necessary for expression of fatty acid oxidation genes [31]. However, the consequences of PPARδ action on PGC-1α in animal models are controversial. In some of these transgenic mice [30] and [31], PGC-1α mRNA expression is not significantly altered in muscle. However, treatment of mice with the PPARδ-specific agonist GW501516 increases the
expression of PGC-1α mRNA, as it does in cultured myocites [24, and the present results]. While this work was in progress, PGC-1α gene expression was shown to be decreased as a consequence of skeletal muscle-selective ablation of PPARδ[32]. Present results further indicate that the induction of PGC-1α expression is amplified by an autoregulatory loop mediated by the coactivation of the PPARδ action on PGC-1α gene transcription by PGC-1α itself. This positive feed-forward control of PGC-1α expression also includes the induction of PPARδ expression by PGC-1α.
