Metabolic Functions of Peroxisome Proliferator-Activated Receptor beta/delta in Skeletal Muscle.

ABSTRACT

Peroxisome proliferator-activated receptors (PPARs) are transcription factors that act as lipid sensors and adapt the metabolic rates of various tissues to the concentration of dietary lipids. PPARs are pharmacological targets for the treatment of metabolic disorders. PPARalpha and PPARgamma are activated by hypolipidemic and insulin-sensitizer compounds, such as fibrates and thiazolidinediones. The roles of PPARbeta/delta in metabolic regulations remained unclear until recently. Treatment of obese monkeys and rodents by specific PPARbeta/delta agonists promoted normalization of metabolic parameters and reduction of adiposity. Recent evidences strongly suggested that some of these beneficial actions are related to activation of fatty acid catabolism in skeletal muscle and also that PPARbeta/delta is involved in the adaptive responses of skeletal muscle to environmental changes, such as long-term fasting or physical exercise, by controlling the number of oxidative myofibers. These observations indicated that PPARbeta/delta agonists might have therapeutic usefulness in metabolic syndrome by increasing fatty acid consumption in skeletal muscle and reducing obesity.