Peroxisome proliferator-activated receptor δ (PPARδ), a novel target site for drug discovery in metabolic syndrome

The development of new treatments for metabolic syndrome is urgent project for decreasing the prevalence of coronary heart disease and diabetes mellitus in the advanced countries. Peroxisome proliferator-activated receptor (PPAR)alpha and gamma agonists have shed light on the treatment of hypertriglyceridemia and type 2 diabetes mellitus, respectively. Among PPARs, analysis of the PPAR delta functions is lagging behind because specific PPAR delta agonists have not been developed. The appearance of new PPAR delta agonists is brightening the prospects for elucidating the physiological role of PPAR delta. PPAR delta is a new target for the treatment of metabolic syndrome. In particular, the fact that fatty acid oxidation and energy dissipation in skeletal muscle and adipose tissue by PPAR delta agonists lead to improved lipid profile, reduced adiposity and insulin sensitivity is a breakthrough. It seems that treatment of PPAR delta agonists operate similarly to the caloric restriction and prolonged exercise. We suggest that the physiological role of PPAR delta may be an indicator for switching from glucose metabolism to fatty acid metabolism. To receive new benefits of PPAR delta agonists against metabolic syndrome by increasing fatty acid consumption in skeletal muscle and adipose tissue, we need to unveil more details on the functions of PPAR delta itself and its agonists in the future. (c) 2006 Elsevier Ltd. All rights reserved.