Regulatory role of peroxisome proliferator-activated receptor delta (PPARδ) in muscle metabolism. A new target for metabolic syndrome treatment?

Peroxisome proliferator-activated receptors (PPARs) are transcription factors involved in both developmental and metabolic functions. There are activated by fatty acids, fatty acid metabolites, and synthetic compounds marketed for their lipid-lowering and antidiabetic actions. It was clearly established that activation of PPARα and PPARγ, by fibrates and thiazolidinediones, respectively, impair metabolic disorders. The implication of the third member of the PPAR family, PPARδ, remained evasive until recently. These past few years, it has been demonstrated that treatment with PPARδ agonists normalizes blood lipids, reduces insulin resistance and adiposity in rodent and primate. Utilization of both cellular and animal models revealed that the nuclear receptor plays a central role in the control of fatty acid burning in adipose tissue and skeletal muscle. Furthermore, PPARδ appeared to be important for adaptive response of skeletal muscle to environmental changes, such as physical exercise.