Pharmacological activation of PPAR[beta] promotes rapid and calcineurin-independent fiber remodeling and angiogenesis in mouse skeletal muscle

Recent studies have shown that administration of peroxisome proliferator-activated receptor-[beta] (PPAR[beta]) agonists enhances fatty acid oxidation in rodent and human skeletal muscle and that musclerestricted PPAR[beta] overexpression affects muscle metabolic profile by increasing oxidative myofiber number, which raises the possibility that PPAR[beta] agonists alter muscle morphology in adult animals. This possibility was examined in this study in which adult mice were treated with a PPAR[beta] agonist, and the resulting changes in myofiber metabolic phenotype and angiogenesis were quantified in tibialis anterior muscles. The findings indicate a muscle remodeling that is completed within 2 days and is characterized by a 1.63-fold increase in oxidative fiber number and by a 1.55-fold increase in capillary number. These changes were associated with a quick and transient upregulation of myogenic and angiogenic markers. Both myogenic and angiogenic responses were dependent on the calcineurin pathway, as they were blunted by cyclosporine A administration. In conclusion, the data indicate that PPAR[beta] activation is associated with a calcineurin-dependent effect on muscle morphology that enhances the oxidative phenotype. myogenesis; metabolism; Type 2 diabetes