Peroxisome Proliferator-Activated Receptors (PPARs)和活化劑(agonists)：文獻回顧

Peroxisome Proliferator-Activated Receptors (PPARs) and Agonists: Review of Literatures

謝純岑(Sung-Kien Sia) ； 楊宜瑱(Yi-Sun Yang) ； 翁國昌(Kwo-Chang Ueng) ； 黃建寧(Chien-Ning Huang)

《內科學誌》 19卷1期 (2008/02) Pp. 14-26

https://doi.org/10.6314/JIMT.2008.19(1).03

摘要

肥胖症(obesity)和代謝症候群(metabolic syndrome)已成爲一種流行病。由肥胖症和代謝症候群所延伸出來的醫療問題，如胰島素阻抗(insulin resistance, IR)、糖尿病(Type 2 DM)、高血壓、高血脂症、心血管疾病等已造成龐大的醫療負擔，更是國人十大死亡原因的重要危險因子。Peroxisome proliferator-activated receptors (PPARs)是細胞核內接受器，主要參與脂質和葡萄糖的代謝。Fibrates和thiazolidinediones (TZDs)分別是市面上的PPARα和PPARγ活化劑，是治療代謝症候群的利器。Fibrates可有效降低三酸甘油脂(TG)、升高高密度脂蛋白膽固醇(HDL-C); TZDs被証實可控制血糖、改善胰島素阻抗；兩者皆具備多重特異效果(pleiotropic effects)，學理上和試驗中發現可以改善發炎反應和血管功能，因而降低心血管風險。最近也有一些雙重(dual) PPARα/γ活化劑(glitazars)進入了Phase Ⅲ臨床試驗階段。Glitazars截取PPARα和PPARγ活化劑的療效，但也逃脫不離PPARs接受器的共同效應(class effects of PPARs)。部分血管緊縮素接受器拮抗劑(an giotensin receptor antagonists, ARBs)近來被發現具備選擇性PPARγ調節活性(selective PPARγ modulation)，可以治療代謝症候群中多項成因。PPARβ／δ是最近被熱烈研究的話題；它擁有除了PPARα和PPARγ活性以外的特性。本文藉由整理一系列PPARs的相關文獻，提供讀者更進一步的了解。

關鍵字

過氧酶體增生活化接受器 ； Fibrates ； Thiazolidinediones ； 血管緊縮素接受器拮抗劑 ； 多重特異效果

並列摘要

Obesity and metabolic syndrome are becoming an epidemic worldwide. The medical problems associated with obesity and metabolic syndrome, including insulin resistance, type 2 diabetes mellitus, hypertension, hyperlipidemia and cardiovascular disease have costed a huge medical financial burden. These are also the noxious members of the Taiwan top-ten leading causes of death. PPARs are intra-nuclear receptors. They act as regulators of lipid and glucose metabolism. Fibrates and thiazolidinediones (TZDs) are marketed PPARα and PPARγ agonist respectively, and are used in the treatment of metabolic syndrome. Fibrates lower serum triglycerides and increase HDL-cholesterol, while TZDs improve glycemic control and insulin resistance. Both ameliorate inflammation and improve vascular function, and have been proved to decrease cardiovascular risks. Recently, many dual PPARα/γ agonists, the glitazars have entered phase Ⅲ clinical trials. Glitazars obtain the beneficial effects of PPARα and PPARγ agonists, as well as the side effects of each PPAR due to class effects. Pan-PPAR and selective PPAR γ modulator (SPPARγ M) have also gained much attention in the literature; however their clinical applications still need further investigation. Angiotensin receptor antagonists (ARBs) have recently been found to posses selective PPAR γ modulation activity, and can be used to treat multiple components of metabolic syndrome. PPARβ/δ has gained most interests recently because it has unique features other than the PPARα and PPARγ activity. We here reviewed some of literatures and summarized them to the readers.

並列關鍵字

Peroxisome Proliferator-Activated Receptor, PPAR ； Fibrates ； Thiazolidinediones ； Angiotensin receptor antagonists, ARBs ； Pleiotropic effects