title: Revisiting PPARγ as a target for the treatment of metabolic disorders.
abstract: As the prevalence of obesity has increased explosively over the last several decades, associated 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 peroxisome proliferator-activated receptors (PPARs) are involved fundamentally in regulating energy homeostasis; thus, they have been considered attractive drug targets for addressing metabolic disorders. Among the PPARs, PPARγ is a master regulator of gene expression for metabolism, inflammation, and other pathways in many cell types, especially adipocytes. It is a physiological receptor of the potent anti-diabetic drugs of the thiazolidinediones (TZDs) class, including rosiglitazone (Avandia). However, TZDs have undesirable and severe side effects, such as weight gain, fluid retention, and cardiovascular dysfunction. Recently, many reports have suggested that PPARγ could be modulated by post-translational modifications (PTMs), and modulation of PTM has been considered as novel approaches for treating metabolic disorders with fewer side effects than the TZDs. In this review, we discuss how PTM of PPARγ may be regulated and issues to be considered in making novel anti-diabetic drugs that can modulate the PTM of PPARγ.
authors.affiliation: Department of Biological Science, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.
authors.forename: Sun-Sil
authors.initials: SS
authors.lastname: Choi
authors.affiliation: Department of Biological Science, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Biological Science, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.
authors.forename: Jang Hyun
authors.initials: JH
authors.lastname: Choi
mesh_terms: D050034:Antidiuretic Agents / Q000627:therapeutic use; D004734:Energy Metabolism; D006801:Humans; D007333:Insulin Resistance; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D050034:Antidiuretic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones