Bile Acids and GPBAR-1: Dynamic Interaction Involving Genes, Environment and Gut Microbiome.
Bile Acids and GPBAR-1: Dynamic Interaction Involving Genes, Environment and Gut Microbiome.
复制标题
胆汁酸和 GPBAR-1：涉及基因、环境和肠道微生物组的动态相互作用。
DOI：
10.3390/nu12123709
复制
发表时间：
2020-11-30
期刊：
影响因子：
5.9
通讯作者：
Wang DQ
中科院分区：
文献类型：
--
作者：
Portincasa P;Di Ciaula A;Garruti G;Vacca M;De Angelis M;Wang DQ
胆汁酸（BA）是在肝脏中由胆固醇合成的两亲性分子。BA通过肠道微生物组的肠道生物转化和重吸收进入门静脉系统以被肝细胞摄取而经历连续的肝肠再循环。BA是有助于膳食脂肪和脂溶性维生素消化和吸收的去污剂分子，但也通过核受体、法尼醇X受体（FXR）和远端肠、肝和肝外组织中的膜相关G蛋白偶联胆汁酸受体1（GPBAR-1）作为重要的信号分子。BA池的疏水-疏水平衡被精细调节以防止BA过载和肝损伤。相比之下，亲水性BA可以是肝保护性的。BA介导的GPBAR-1激活的最终作用尚不清楚，但该受体可能在保护残肝和维持胆汁稳态方面发挥作用。此外，GPBAR-1作用于炎症、胆管上皮屏障通透性、BA池疏水性和正弦血流中涉及的途径。最近的证据表明，环境因素影响GPBAR-1基因的表达。因此，靶向GPBAR-1可能会改善肝脏保护，通过一级预防措施促进有益的代谢作用。在这里，我们讨论了与BA效应相关的复杂途径，GPBAR-1的信号传导特性，肝损伤机制，基因-环境相互作用和治疗方面。
Bile acids (BA) are amphiphilic molecules synthesized in the liver from cholesterol. BA undergo continuous enterohepatic recycling through intestinal biotransformation by gut microbiome and reabsorption into the portal tract for uptake by hepatocytes. BA are detergent molecules aiding the digestion and absorption of dietary fat and fat-soluble vitamins, but also act as important signaling molecules via the nuclear receptor, farnesoid X receptor (FXR), and the membrane-associated G protein-coupled bile acid receptor 1 (GPBAR-1) in the distal intestine, liver and extra hepatic tissues. The hydrophilic-hydrophobic balance of the BA pool is finely regulated to prevent BA overload and liver injury. By contrast, hydrophilic BA can be hepatoprotective. The ultimate effects of BA-mediated activation of GPBAR-1 is poorly understood, but this receptor may play a role in protecting the remnant liver and in maintaining biliary homeostasis. In addition, GPBAR-1 acts on pathways involved in inflammation, biliary epithelial barrier permeability, BA pool hydrophobicity, and sinusoidal blood flow. Recent evidence suggests that environmental factors influence GPBAR-1 gene expression. Thus, targeting GPBAR-1 might improve liver protection, facilitating beneficial metabolic effects through primary prevention measures. Here, we discuss the complex pathways linked to BA effects, signaling properties of the GPBAR-1, mechanisms of liver damage, gene-environment interactions, and therapeutic aspects.
登录
查看更多内容
影响因子：
3.7
作者：
Cipriani S;Mencarelli A;Chini MG;Distrutti E;Renga B;Bifulco G;Baldelli F;Donini A;Fiorucci S
通讯作者：
Fiorucci S
影响因子：
3.8
作者：
Cheng, Sunny Lihua;Li, Xueshu;Cui, Julia Yue
通讯作者：
Cui, Julia Yue
影响因子：
29.4
作者：
Denson, LA;Sturm, E;Karpen, SJ
通讯作者：
Karpen, SJ
影响因子：
6
作者：
Bhushan, Bharat;Borude, Prachi;Apte, Udayan
通讯作者：
Apte, Udayan
影响因子：
6.5
作者：
de Boer, Jan Freark;Verkade, Esther;Kuipers, Folkert
通讯作者：
Kuipers, Folkert