Floyd Z Elizabeth, Stephens Jacqueline M
Ubiquitin Biology Laboratory, Pennington Biomedical Research Resaerch Center, Louisiana Sate University Systems, Baton Rouge, LA 70808, USA.
Biochim Biophys Acta. 2012 Jul;1822(7):1090-5. doi: 10.1016/j.bbadis.2012.03.014. Epub 2012 Apr 4.
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 PPARγ. PPARγ 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, PPARγ 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 PPARγ activity have been identified and studied. These covalent modifications include phosphorylation, ubiquitylation, O-GlcNAcylation and SUMOylation. Covalent modifications of PPARγ represent key regulatory mechanisms that control both PPARγ protein stability and transcriptional activity. A variety of PPARγ transgenic models, including mice heterozygous for PPARγ, have demonstrated the importance of PPARγ expression in glucose homeostasis and insulin resistance. In the following review, we have highlighted the regulation of PPARγ by covalent modifications, the interplay between these interactions and how these post-translational modifications impact metabolic disease states.
脂肪细胞是高度特化的细胞，在脂质稳态和能量平衡维持中发挥核心作用。肥胖是脂肪组织的过度蓄积，是2型糖尿病（T2DM）、心血管疾病和高血压发生的主要危险因素。多项研究表明，肥胖和T2DM可能与控制PPARγ表达和转录活性的调节机制失灵有关。PPARγ是一种核激素受体，在控制脂肪细胞分化和发育中起主控开关的作用。PPARγ在控制葡萄糖稳态和胰岛素敏感性方面也很重要，它是一种依赖配体的转录因子，是抗糖尿病噻唑烷二酮类药物（TZDs）的功能性受体。在过去十五年中，已鉴定并研究了多种对PPARγ活性的共价修饰。这些共价修饰包括磷酸化、泛素化、O-连接的N-乙酰葡糖胺化和SUMO化。PPARγ的共价修饰代表了控制PPARγ蛋白稳定性和转录活性的关键调节机制。多种PPARγ转基因模型，包括PPARγ杂合小鼠，已证明PPARγ表达在葡萄糖稳态和胰岛素抵抗中的重要性。在以下综述中，我们重点介绍了共价修饰对PPARγ的调节、这些相互作用之间的相互影响以及这些翻译后修饰如何影响代谢疾病状态。
