Department of Integrative Medical Sciences, Northeastern Ohio Universities College of Medicine, Rootstown, OH 44272, USA.
PPAR Res. 2009;2009:501739. doi: 10.1155/2009/501739. Epub 2009 Jul 14.
Bile acids are amphipathic molecules synthesized from cholesterol in the liver. Bile acid synthesis is a major pathway for hepatic cholesterol catabolism. Bile acid synthesis generates bile flow which is important for biliary secretion of free cholesterol, endogenous metabolites, and xenobiotics. Bile acids are biological detergents that facilitate intestinal absorption of lipids and fat-soluble vitamins. Recent studies suggest that bile acids are important metabolic regulators of lipid, glucose, and energy homeostasis. Agonists of peroxisome proliferator-activated receptors (PPARα, PPARγ, PPARδ) regulate lipoprotein metabolism, fatty acid oxidation, glucose homeostasis and inflammation, and therefore are used as anti-diabetic drugs for treatment of dyslipidemia and insulin insistence. Recent studies have shown that activation of PPARα alters bile acid synthesis, conjugation, and transport, and also cholesterol synthesis, absorption and reverse cholesterol transport. This review will focus on the roles of PPARs in the regulation of pathways in bile acid and cholesterol homeostasis, and the therapeutic implications of using PPAR agonists for the treatment of metabolic syndrome.
胆汁酸是在肝脏中从胆固醇合成的两亲分子。胆汁酸合成是肝脏胆固醇分解代谢的主要途径。胆汁酸合成产生胆汁流，这对于胆汁中游离胆固醇、内源性代谢物和外源性化合物的分泌很重要。胆汁酸是促进脂质和脂溶性维生素吸收的生物清洁剂。最近的研究表明，胆汁酸是脂质、葡萄糖和能量稳态的重要代谢调节剂。过氧化物酶体增殖物激活受体 (PPARα、PPARγ、PPARδ) 的激动剂调节脂蛋白代谢、脂肪酸氧化、葡萄糖稳态和炎症，因此被用作治疗血脂异常和胰岛素抵抗的抗糖尿病药物。最近的研究表明，PPARα 的激活改变了胆汁酸的合成、结合和转运，以及胆固醇的合成、吸收和逆向胆固醇转运。这篇综述将重点介绍 PPAR 在调节胆汁酸和胆固醇稳态途径中的作用，以及使用 PPAR 激动剂治疗代谢综合征的治疗意义。
