An overview on biological mechanisms of PPARs

被引:561
作者
Kota, BP [1 ]
Huang, THW [1 ]
Roufogalis, BD [1 ]
机构
[1] Univ Sydney, Fac Pharm, Sydney, NSW 2006, Australia
关键词
nuclear receptors; PPARs; diabetes; inflammation; atherosclerosis; cancer;
D O I
10.1016/j.phrs.2004.07.012
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Peroxisome proliferator activated receptors (PPARs) are transcriptional factors belonging to the ligand-activated nuclear receptor superfamily. They are ubiquitously expressed throughout the body. On activation by endogenously secreted prostaglandins and fatty acids, they initiate transcription of an array of genes that are involved in energy homeostasis. So far, three major types have been identified, namely PPAR-alpha, PPAR-beta/delta and PPAR-gamma. PPAR-alpha and PPAR-gamma are crucial for lipid and glucose metabolism, respectively. Although limited information is available on PPAR-beta biological functions, recent studies have shown that PPAR-alpha also regulates glucose metabolism and fatty acid oxidation. The discovery of PPAR-alpha agonists such as fibrates and PPAR-gamma agonists such as thiozolidinediones enables recognition of the mechanisms involved in ameliorating the adverse effects of chronic disorders such as atherosclerosis and diabetes. In addition, PPARs are also involved in the regulation of various types of tumours, inflammation, cardiovascular diseases and infertility. The importance of these transcription factors in physiology and pathophysiology has instigated much research in this field. In this article, structural features of PPARs, their gene transcription mechanisms and recent developments in the discovery of their biological functions are reviewed. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:85 / 94
页数:10
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