过氧化物酶体增殖物激活受体在肥胖、糖尿病和炎症中的治疗作用

Therapeutic role of peroxisome proliferator-activated receptors in obesity, diabetes and inflammation.

作者信息

Ram Vishnu Ji

机构信息

Medicinal Chemistry Division, Central Drug Research Institute, Lucknow 226001, India.

出版信息

Prog Drug Res. 2003;60:93-132. doi: 10.1007/978-3-0348-8012-1_3.

DOI:10.1007/978-3-0348-8012-1_3

PMID:12790340

Abstract

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family and play a significant role in regulation of lipid metabolism, hepatic peroxisomal enzyme expression, insulin sensitivity and glucose homeostasis. PPARs have been classified into three subtypes encoded by different genes: PPARalpha (NR1C1), PPARdelta (NR1C2), and PPARgamma (NR1C3). Each subtype of PPARs appears to be differently expressed in a tissue-specific manner because of their binding to specific consensus DNA sequences, known as PPREs (peroxisome proliferator response elements). Thus, PPARs have emerged as potential molecular targets for the design and synthesis of a different class of compounds, considering the conformation of receptors for the treatment of human metabolic disorders. This review covers the rapid progress made in functional analysis of PPARs and progress made towards the identification of ligands for each subtype receptor.

摘要

过氧化物酶体增殖物激活受体（PPARs）是核受体家族的成员，在脂质代谢、肝脏过氧化物酶体酶表达、胰岛素敏感性和葡萄糖稳态的调节中发挥重要作用。PPARs已被分为由不同基因编码的三种亚型：PPARα（NR1C1）、PPARδ（NR1C2）和PPARγ（NR1C3）。由于PPARs各亚型与特定的共有DNA序列（称为过氧化物酶体增殖物反应元件，PPREs）结合，它们似乎以组织特异性方式呈现不同的表达。因此，考虑到用于治疗人类代谢紊乱的受体构象，PPARs已成为设计和合成不同类化合物的潜在分子靶点。本综述涵盖了PPARs功能分析方面取得的快速进展以及在鉴定各亚型受体配体方面取得的进展。