Nutraceuticals as Ligands of PPARγ

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors that respond to several exogenous and endogenous ligands by modulating genes related to lipid, glucose, and insulin homeostasis. PPARγ, expressed in adipose tissue and liver, regulates lipid storage and glucose metabolism and is the target of type 2 diabetes drugs, thiazolidinediones (TZDs). Due to high levels of toxicity associated with the first generation TZDs, troglitazone (Rezulin), rosiglitazone (Avandia), and pioglitazone (Actos), there is a renewed search for newer PPAR drugs that exhibit better efficacy but lesser toxicity. In recent years, there has been a definite increase in the consumption of dietary supplements among diabetics, due to the possible health benefits associated with these nutraceutical components. With this impetus, investigations into alternative natural ligands of PPARs has also risen. This review highlights some of the dietary compounds (dietary lipids, isoflavones, and other flavanoids) that bind and transactivate PPARγ. A better understanding of the physiological effects of this PPAR activation by nutraceuticals and the availability of high-throughput technologies should lead to the discovery of less toxic alternatives to the PPAR drugs currently on the market.