PGC1α expression is controlled in skeletal muscles by PPARβ, whose ablation results in fiber-type switching, obesity, and type 2 diabetes

SummaryMice in which peroxisome proliferator-activated receptor β (PPARβ) is selectively ablated in skeletal muscle myocytes were generated to elucidate the role played by PPARβ signaling in these myocytes. These somatic mutant mice exhibited a muscle fiber-type switching toward lower oxidative capacity that preceded the development of obesity and diabetes, thus demonstrating that PPARβ is instrumental in myocytes to the maintenance of oxidative fibers and that fiber-type switching is likely to be the cause and not the consequence of these metabolic disorders. We also show that PPARβ stimulates in myocytes the expression of PGC1α, a coactivator of various transcription factors, known to play an important role in slow muscle fiber formation. Moreover, as the PGC1α promoter contains a PPAR response element, the effect of PPARβ on the formation and/or maintenance of slow muscle fibers can be ascribed, at least in part, to a stimulation of PGC1α expression at the transcriptional level.