Regulation of Skeletal Muscle Physiology and Metabolism by Peroxisome Proliferator-Activated Receptor δ

Agonists directed against the alpha and gamma isoforms of the peroxisome proliferator-activated receptors (PPARs) have become important for the respective treatment of hypertriglyceridemia and insulin resistance associated with metabolic disease. PPAR delta is the least well characterized of the three PPAR isoforms. Skeletal muscle insulin resistance is a primary risk factor for the development of type 2 diabetes. There is increasing evidence that PPAR delta is an important regulator of skeletal muscle metabolism, in particular, muscle lipid oxidation, highlighting the potential utility of this isoform as a drug target. In addition, PPAR delta seems to be a key regulator of skeletal muscle fiber type and a possible mediator of the adaptations noted in skeletal muscle in response to exercise. In this review we summarize the current status regarding the regulation, and the metabolic effects, of PPAR delta in skeletal muscle.