遗传 ›› 2019, Vol. 41 ›› Issue (5): 365-374.doi: 10.16288/j.yczz.19-011

• 综述 • 上一篇    下一篇

胆汁酸的合成调控及其在生理与病理中的功能机制

刘笑,王琰()   

  1. 武汉大学生命科学学院,细胞稳态湖北省重点实验室,武汉 430072
  • 收稿日期:2019-01-09 修回日期:2019-03-18 出版日期:2019-05-20 发布日期:2019-03-25
  • 通讯作者: 王琰 E-mail:Wang.y@whu.edu.cn
  • 作者简介:刘笑,硕士研究生,专业方向：脂类代谢。E-mail: 2016202040152@whu.edu.cn
  • 基金资助:
    国家自然科学基金项目(91754101)

An overview of bile acid synthesis and its physiological and pathological functions

Xiao Liu,Yan Wang()   

  1. Hubei Province Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China
  • Received:2019-01-09 Revised:2019-03-18 Online:2019-05-20 Published:2019-03-25
  • Contact: Wang Yan E-mail:Wang.y@whu.edu.cn
  • Supported by:
    National Natural Science Foundation of China(91754101)

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摘要：

胆汁酸是一类胆固醇的代谢物,在机体胆固醇与能量代谢平衡和小肠营养物质吸收等方面起着重要作用。肝脏是合成胆汁酸的主要场所。饥饿条件下,胆汁酸从肝脏分泌进入胆管并被储存到胆囊;进食后胆囊收缩,贮存的胆汁酸被排出进入小肠。在小肠中,95%的胆汁酸会被小肠重新吸收,通过肝门静脉返回肝脏,这一过程被称为胆汁酸的肝肠循环。胆汁酸一方面作为乳化剂促进小肠中脂类等物质的吸收及转运,同时也作为重要的信号分子与多种受体结合,包括核受体法呢醇X受体(farnesoid X receptor, FXR)、维生素D受体(vitamin D receptor, VDR)、孕烷X受体(pregnane X receptor, PXR)以及细胞膜表面受体G蛋白偶联受体(cell membrane surface receptor-G protein coupled receptor, TGR5)等,在调节体内胆汁酸的代谢平衡、糖脂代谢与能量代谢平衡等方面发挥重要作用。肝细胞生长因子(hepatocyte growth factor, HGF)、白介素1-β (interleukin-1β, IL-1β)及肿瘤坏死因子(tumor necrosis factor α, TNF-α)等协同作用构成了胆汁酸合成的精密调控网络。本文主要综述了胆汁酸的合成调控及其功能方面的最新研究进展,旨在为胆汁酸代谢相关研究提供参考。

关键词: 胆汁酸, 胆固醇7α羟化酶;, 法呢醇X受体, 代谢, 调控

Abstract:

Bile acids are a class of cholesterol derivatives that play important roles in cholesterol and energy homeostasis and intestinal nutrition absorption. Bile acids are mainly synthesized in the liver. During fasting, bile acids are secreted from the liver and stored in the gallbladder. After a meal, the stored bile acids are released into small intestines. In the intestine, about 95% of bile acids will be re-absorbed and travel back into the liver through port veins, which is called bile acid enterohepatic circulation. This enterohepatic circulation of bile acids plays important roles in the emulsification and intestinal absorption of lipids and other nutrition. On the other hand, bile acids function as ligands for a number of receptors, such as farnesoid X receptor (FXR), proterane X receptor (PXR), vitamin D receptor (VDR) and cell membrane surface receptor-G protein coupled receptor (TGR5), which play important roles from metabolic homeostasis to innate immunity. A number of cytokines such as hepatocyte growth factor (HGF), interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) regulate the homeostasis of bile acids. In the current review, we will summarize the recent progress in the regulation of bile acid synthesis and its physiological and pathological functions from energy homeostasis to innate immunity and cancer progression to provide a reference for the study of bile acid metabolism.

Key words: bile acid, CYP7A1, FXR, metabolism, regulation