PPAR delta: an uncompletely known nuclear receptor

Peroxisome proliferator-activated receptors (PPAR) mediate some of the transcriptional effects of fatty acids and control many physiological functions, especially in the field of development and metabolism. Three isotypes are known, alpha, gamma, and B/delta. Roles of PPAR alpha and PPARgamma are now quite well-known, particularly since their pharmacologic ligands have been marketed, respectively the lipid-normalizing class of fibrates and the antidiabetic class of thiazolidinediones (glitazones). However, functions of PPARdelta are uncompletely known to date, but some recent data enlight its role in the regulation of fatty acid oxidation in several tissues, such as skeletal muscle and adipose tissue. Overexpression of PPARdelta using a transgenic murine model promotes an increase of muscle oxidative capability. This is accompanied by a redistribution of fatty acid flux, redirected from adipose tissue towards skeletal muscle. Finally, adipose mass is reduced, due to a decreased adipocyte size. These data strongly suggest that PPARdelta play a major role in the metabolic adaptations to western diet characterized by an excessive amount of saturated fat. Considering the metabolic properties of the two other PPAR isotypes, alpha and gamma, it is likely that the three PPAR isotypes have complementary effects in the pathophysiology of obesity and metabolic syndrome. Future therapeutical perspectives in this field should consider combined treatment, adding delta agonists (for all that their safety will be established) to the already available alpha and gamma agonists.