Revisiting PPAR gamma as a target for the treatment of metabolic disorders

Abstract

As the prevalence of obesity has explosively increased in the last several decades, the associate metabolic disorders, including type 2 diabetes, dyslipidemia, hypertension, and cardiovascular diseases have been also increased. Thus, new strategies for preventing and treating them are needed. The nuclear receptor peroxisome proliferator-activated receptors (PPARs) involve fundamentally in regulating energy homeostasis, thus they are considered as attractive drug targets for curing metabolic disorders. Among PPARs, PPARγ is a master regulator of gene expression of metabolism, inflammation, and other pathways in many cell types, especially adipocytes. It is a physiological receptor of the potent anti-diabetic drugs of thiazolidinediones (TZDs) class, including rosiglitazone (Avandia). However, TZDs have undesirable and severe side effects such as weight gain, fluid retention, and cardiovascular dysfunctions. Recently, many reports have been suggested that PPARγ could be modulated by post-translational modifications (PTMs), and modulations of PTMs are considered as novel approaches for curing metabolic disorders with fewer side effects what TZDs have. In this review, we will discuss how PTMs of PPARγ can be regulated and what we have to consider for making novel anti-diabetic drugs which can modulate PTMs of PPARγ.