过氧化物酶体增殖物激活受体γ与代谢性疾病

Peroxisome proliferator-activated receptor gamma and metabolic disease.

作者信息

Willson T M, Lambert M H, Kliewer S A

机构信息

GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, North Carolina 27709, USA.

出版信息

Annu Rev Biochem. 2001;70:341-67. doi: 10.1146/annurev.biochem.70.1.341.

DOI:10.1146/annurev.biochem.70.1.341

PMID:11395411

Abstract

The nuclear peroxisome proliferator-activated receptor gamma (PPAR gamma) is a transcription factor that is activated by polyunsaturated fatty acids and their metabolites and is essential for fat cell formation. Although obesity is a strong risk factor for type 2 diabetes mellitus and other metabolic diseases, potent PPAR gamma activators such as the glitazone drugs lower glucose and lipid levels in patients with type 2 diabetes and also have antiatherosclerotic and antihypertensive effects. We review recent studies providing insight into the paradoxical relationship between PPAR gamma and metabolic disease. We also review recent advances in understanding the structural basis for PPAR gamma activation by ligands. The unusual ligand-binding properties of PPAR gamma suggest that it will be possible to discover new chemical classes of receptor "modulators" with distinct pharmacological activities for the treatment of type 2 diabetes and other metabolic diseases.

摘要

核过氧化物酶体增殖物激活受体γ（PPARγ）是一种转录因子，可被多不饱和脂肪酸及其代谢产物激活，对脂肪细胞形成至关重要。尽管肥胖是2型糖尿病和其他代谢性疾病的强风险因素，但强效PPARγ激活剂如格列酮类药物可降低2型糖尿病患者的血糖和血脂水平，还具有抗动脉粥样硬化和降压作用。我们综述了近期研究，这些研究为深入了解PPARγ与代谢性疾病之间的矛盾关系提供了见解。我们还综述了在理解配体激活PPARγ的结构基础方面的最新进展。PPARγ不同寻常的配体结合特性表明，有可能发现具有不同药理活性的新型受体“调节剂”化学类别，用于治疗2型糖尿病和其他代谢性疾病。