Tratamiento de enfermedades metabólicas mediante la modulación del PPARγ

Metabolic syndrome and related disorders, such as obesity, type 2 diabetes mellitus, hypertension and dyslipidemia, are characterized by a progressive resistance of glucose metabolism to the action of insulin, termed insulin resistance. Consequently, improving insulin resistance is a major therapeutic goal. Peroxisome proliferatoractivated receptor g (PPARg) is a nuclear receptor, which plays a key role in lipid and glucose homeostasis. The PPARg agonists, thiazolidinediones (TZD), are powerful drugs that are clinically used to treat insulin resistance and hyperglycemia. Moreover, these compounds have additional lipid-independent anti-inflammatory effects, suggesting that they might also be useful for the treatment and prevention of atherosclerosis. However, given the numerous side effects observed with TZD treatment, novel classes of PPARg modulators have been designed and developed. The present review will focus on the different compounds that have been shown to bind and modulate PPARg activity, especially TZD, and the potential benefits of pharmacological modulation of PPARg to treat human metabolic disease.