Controlling a master switch of adipocyte development and insulin sensitivity: Covalent modifications of PPARγ

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1822

Review

Stephens, Jacqueline M.¹ 

[1] Louisiana State Univ, Pennington Biomed Res Ctr, Ubiquitin Biol Lab, Baton Rouge, LA 70808 USA

关键词: Adipocyte;    PPAR gamma;    Adipogenesis;    Ubiquitylation;    SUMOylation;   

DOI  :  10.1016/j.bbadis.2012.03.014

来源: Elsevier

【 摘 要 】

Adipocytes are highly specialized cells that play a central role in lipid homeostasis and the maintenance of energy balance. Obesity, an excessive accumulation of adipose tissue, is a major risk factor for the development of Type 2 diabetes mellitus (T2DM), cardiovascular disease, and hypertension. A variety of studies suggest that obesity and T2DM can be linked to a breakdown in the regulatory mechanisms that control the expression and transcriptional activity of PPAR gamma. PPAR gamma is a nuclear hormone receptor that functions as a master switch in controlling adipocyte differentiation and development. Also important in controlling glucose homeostasis and insulin sensitivity. PPAR gamma is a ligand-dependent transcription factor that is the functional receptor for the anti-diabetic thiazolidinediones (TZDs). In the last fifteen years, a variety of covalent modifications of PPAR gamma activity have been identified and studied. These covalent modifications include phosphorylation, ubiquitylation, O-GlcNAcylation and SUMOylation. Covalent modifications of PPAR gamma represent key regulatory mechanisms that control both PPAR gamma protein stability and transcriptional activity. A variety of PPAR gamma transgenic models, including mice heterozygous for PPAR gamma, have demonstrated the importance of PPAR gamma expression in glucose homeostasis and insulin resistance. In the following review, we have highlighted the regulation of PPAR gamma by covalent modifications, the interplay between these interactions and how these post-translational modifications impact metabolic disease states. (c) 2012 Elsevier B.V. All rights reserved.

【 授权许可】

Free