Kota Bhavani Prasad, Huang Tom Hsun-Wei, Roufogalis Basil D
Faculty of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia.
Pharmacol Res. 2005 Feb;51(2):85-94. doi: 10.1016/j.phrs.2004.07.012.
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-beta 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.
过氧化物酶体增殖物激活受体（PPARs）是属于配体激活核受体超家族的转录因子。它们在全身广泛表达。在被内源性分泌的前列腺素和脂肪酸激活后，它们启动一系列参与能量稳态的基因的转录。到目前为止，已鉴定出三种主要类型，即PPAR-α、PPAR-β/δ和PPAR-γ。PPAR-α和PPAR-γ分别对脂质和葡萄糖代谢至关重要。尽管关于PPAR-β生物学功能的信息有限，但最近的研究表明，PPAR-β也调节葡萄糖代谢和脂肪酸氧化。贝特类等PPAR-α激动剂和噻唑烷二酮类等PPAR-γ激动剂的发现，使人们能够认识到改善动脉粥样硬化和糖尿病等慢性疾病不良反应所涉及的机制。此外，PPARs还参与多种类型肿瘤、炎症、心血管疾病和不孕症的调节。这些转录因子在生理学和病理生理学中的重要性激发了该领域的大量研究。本文综述了PPARs的结构特征、基因转录机制及其生物学功能发现的最新进展。
