PPAR家族及其与代谢综合征的关系

PPAR Family and Its Relationship to Metabolic Syndrome

过氧化物酶体增殖物激活受体 (peroxisomeproliferator activatedreceptors ,PPARs)是配体激活的转录因子核受体超家族成员之一。目前已知有三种亚型 :PPARα、 β δ和 γ。它们在脂肪生成、脂质代谢、胰岛素敏感性、炎症和血压调节中起着关键作用 ,因而近年来倍受关注。越来越多的研究表明 ,PPARs与代谢综合征 ,包括胰岛素抵抗、糖耐量受损、2型糖尿病、肥胖、高脂血症、高血压病、动脉粥样硬化和蛋白尿之间存在因果关系。重要的是 ,PPARα的激动剂如贝丁酸类降脂药 (Fi brate)和PPARγ的激动剂如噻唑烷二酮 (Thiazolidinedione ,TZD)均已被证实有改善代谢综合征的作用。此外 ,三种PPAR亚型在 2型糖尿病及糖尿病肾病的发展中均有重要作用。不断增加的证据提示 ,PPARs有可能成为代谢综合征及其相关并发症的潜在治疗靶点。本文将就PPARs的生物学活性、配体选择性和生理学功能作一综述 。

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone re-ceptor superfamily of ligand-activated transcription factors. Three PPAR isoforms, designated PPARα, -β/δ, and -γ, have been identified and attracted enormous attention due to the key role these receptors play in regulating adipogenesis, lipid metabolism, insulin sensitivity, inflammation and blood pressure. Growing evidence points to a causative relationship between PPAR activity and the metabolic syndrome, including insulin resistance, glucose intolerance or type II diabetes, obesity, dyslipidemia, hypertension, atherosclerosis, and albuminuria. Importantly, both PPARα activators such as fibric acid class of hypolipidemic drugs and PPARγ agonists including antidiabetic thiazolidinediones (TZDs) have been proved to be effective for improving metabolic syndrome. All three PPAR isoforms appear to play important roles in the development of type II diabetes and diabetic nephropathy. Accumulating data has begun to emerge suggesting PPARs may serve as potential therapeutic targets for treating the metabolic syndrome and its related complications. Here we review the literature pertaining to the action, ligand selectivity and physiological role of PPARs. Particular emphasis is placed on their pathogenic roles in the metabolic syndrome and the therapeutic utility of PPAR modulators in the treatment of type II diabetes.