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Revisiting PPARγ as a target for the treatment of metabolic disorders

期刊

BMB REPORTS
卷 47, 期 11, 页码 599-608

出版社

KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY
DOI: 10.5483/BMBRep.2014.47.11.174

关键词

Insulin sensitivity; Metabolic disorders; Post translational modification (PTMs); PPAR gamma; Thiazolidinediones (TZDs)

资金

  1. Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [NRF-2013R1A1A2060283, NRF-2012R1A1A1015407]
  2. Ulsan National Institute of Science and Technology (UNIST) [1.130088.01]
  3. National Research Foundation of Korea [2012R1A1A1015407, 22A20130012280] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

向作者/读者索取更多资源

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, PPAR. 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 PPAR gamma 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 PPAR gamma may be regulated and issues to be considered in making novel anti-diabetic drugs that can modulate the PTM of PPAR gamma.

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