Chiang John Y L, Ferrell Jessica M
Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA.
Liver Res. 2020 Jun;4(2):47-63. doi: 10.1016/j.livres.2020.05.001. Epub 2020 Jun 3.
Cholesterol 7 alpha-hydroxylase (CYP7A1, EC1.14) is the first and rate-limiting enzyme in the classic bile acid synthesis pathway. Much progress has been made in understanding the transcriptional regulation of gene expression and the underlying molecular mechanisms of bile acid feedback regulation of CYP7A1 and bile acid synthesis in the last three decades. Discovery of bile acid-activated receptors and their roles in the regulation of lipid, glucose and energy metabolism have been translated to the development of bile acid-based drug therapies for the treatment of liver-related metabolic diseases such as alcoholic and non-alcoholic fatty liver diseases, liver cirrhosis, diabetes, obesity and hepatocellular carcinoma. This review will provide an update on the advances in our understanding of the molecular biology and mechanistic insights of the regulation of CYP7A1 in bile acid synthesis in the last 40 years.
胆固醇7α-羟化酶（CYP7A1，EC1.14）是经典胆汁酸合成途径中的首个限速酶。在过去三十年里，我们对该基因表达的转录调控以及CYP7A1胆汁酸反馈调节和胆汁酸合成的潜在分子机制的理解取得了很大进展。胆汁酸激活受体的发现及其在脂质、葡萄糖和能量代谢调节中的作用已转化为基于胆汁酸的药物疗法的开发，用于治疗与肝脏相关的代谢性疾病，如酒精性和非酒精性脂肪性肝病、肝硬化、糖尿病、肥胖症和肝细胞癌。本综述将介绍过去40年里我们在CYP7A1胆汁酸合成调控的分子生物学及机制研究方面的进展。
