Peroxisome proliferator-activated receptor beta/delta: a master regulator of metabolic pathways in skeletal muscle

Skeletal muscle is considered to be a major site of energy expenditure and thus is important in regulating events affecting metabolic disorders. Over the years, both in vitro and in vivo approaches have established the role of peroxisome proliferator-activated receptor-beta/delta (PPAR beta/delta) in fatty acid metabolism and energy expenditure in skeletal muscles. Pharmacological activation of PPAR beta/delta by specific ligands regulates the expression of genes involved in lipid use, triglyceride hydrolysis, fatty acid oxidation, energy expenditure, and lipid efflux in muscles, in turn resulting in decreased body fat mass and enhanced insulin sensitivity. Both the lipid-lowering and the anti-diabetic effects exerted by the induction of PPAR beta/delta result in the amelioration of symptoms of metabolic disorders. This review summarizes the action of PPARb beta/delta activation in energy metabolism in skeletal muscles and also highlights the unexplored pathways in which it might have potential effects in the context of muscular disorders. Numerous preclinical studies have identified PPAR beta/delta as a probable potential target for therapeutic interventions. Although PPAR beta/delta agonists have not yet reached the market, several are presently being investigated in clinical trials.