Peroxisome proliferator-activated receptor (PPAR) beta/delta: a new potential therapeutic target for the treatment of metabolic syndrome.

ABSTRACT

Metabolic syndrome is defined as the clustering of multiple metabolic abnormalities, including abdominal obesity, dyslipidemia (high serum triglycerides and low serum HDL-cholesterol levels), glucose intolerance and hypertension. The pathophysiology underlying metabolic syndrome involves a complex interaction of crucial factors, but two of these, insulin resistance and obesity (especially visceral obesity), play a major role. The nuclear receptors Peroxisome Proliferator-Activated Receptors (PPAR)alpha and PPARgamma are therapeutic targets for hypertriglyceridemia and insulin resistance, respectively. Evidence is now emerging that the PPARbeta/delta; isotype is a potential pharmacological target for the treatment of disorders associated with metabolic syndrome. PPARbeta/delta; activation increases lipid catabolism in skeletal muscle, heart and adipose tissue and improves the serum lipid profile and insulin sensitivity in several animal models. In addition, PPARbeta/delta; ligands prevent weight gain and suppress macrophage-derived inflammation. These data are promising and indicate that PPARbeta/delta; ligands may become a therapeutic option for the treatment of metabolic syndrome. However, clinical trials in humans assessing the efficacy and safety of these drugs should confirm these promising perspectives in the treatment of the metabolic syndrome.