Bile acid receptors in non-alcoholic fatty liver disease

被引:159
作者
Li, Yuanyuan [1 ]
Jadhav, Kavita [1 ]
Zhang, Yanqiao [1 ]
机构
[1] Northeast Ohio Med Univ, Dept Integrat Med Sci, Rootstown, OH 44272 USA
关键词
FXR; TGR5; Triglyceride; Cholesterol; Inflammation; FARNESOID-X-RECEPTOR; SMALL HETERODIMER PARTNER; PPAR-ALPHA; ACYLCARNITINE HYDROLASE; TRIGLYCERIDE LEVELS; INSULIN-RESISTANCE; GENE-EXPRESSION; FXR; ACTIVATION; TGR5;
D O I
10.1016/j.bcp.2013.08.015
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Accumulating data have shown that bile acids are important cell signaling molecules, which may activate several signaling pathways to regulate biological processes. Bile acids are endogenous ligands for the farnesoid X receptor (FXR) and TGR5, a G-protein coupled receptor. Gain- and loss-of-function studies have demonstrated that both FXR and TGR5 play important roles in regulating lipid and carbohydrate metabolism and inflammatory responses. Importantly, activation of FXR or TGR5 lowers hepatic triglyceride levels and inhibits inflammation. Such properties of FXR or TGR5 have indicated that these two bile acid receptors are ideal targets for treatment of non-alcoholic fatty liver disease, one of the major health concerns worldwide. In this article, we will focus on recent advances on the role of both FXR and TGR5 in regulating hepatic triglyceride metabolism and inflammatory responses under normal and disease conditions. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码:1517 / 1524
页数:8
相关论文
共 72 条
[1]
Farnesoid X receptor targeting to treat nonalcoholic steatohepatitis [J].
Adorini, Luciano ;
Pruzanski, Mark ;
Shapiro, David .
DRUG DISCOVERY TODAY, 2012, 17 (17-18) :988-997
[2]
Molecular mechanisms and therapeutic targets in steatosis and steatohepatitis [J].
Anderson, Nora ;
Borlak, Juergen .
PHARMACOLOGICAL REVIEWS, 2008, 60 (03) :311-357
[3]
Syndecan-1 expression is regulated in an isoform-specific manner by the farnesoid-X receptor [J].
Anisfeld, AM ;
Kast-Woelbern, HR ;
Meyer, ME ;
Jones, SA ;
Zhang, YQ ;
Williams, KJ ;
Willson, T ;
Edwards, PA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (22) :20420-20428
[4]
Kupffer cells in non-alcoholic fatty liver disease: The emerging view [J].
Baffy, Gyoergy .
JOURNAL OF HEPATOLOGY, 2009, 51 (01) :212-223
[5]
CHENODEOXYCHOLIC ACID THERAPY FOR HYPERTRIGLYCERIDEMIA IN MEN [J].
BATESON, MC ;
MACLEAN, D ;
EVANS, JR ;
BOUCHIER, IAD .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1978, 5 (03) :249-254
[6]
Free fatty acids repress small heterodimer partner (SHP) activation and adiponectin counteracts bile acid-induced liver injury in superobese patients with nonalcoholic steatohepatitis [J].
Bechmann, Lars P. ;
Kocabayoglu, Peri ;
Sowa, Jan-Peter ;
Sydor, Svenja ;
Best, Jan ;
Schlattjan, Martin ;
Beilfuss, Anja ;
Schmitt, Johannes ;
Hannivoort, Rebekka A. ;
Kilicarslan, Alpaslan ;
Rust, Christian ;
Berr, Frieder ;
Tschopp, Oliver ;
Gerken, Guido ;
Friedman, Scott L. ;
Geier, Andreas ;
Canbay, Ali .
HEPATOLOGY, 2013, 57 (04) :1394-1406
[7]
Regulation of hepatic metabolic pathways by the orphan nuclear receptor SHP [J].
Boulias, K ;
Katrakili, N ;
Bamberg, K ;
Underhill, P ;
Greenfield, A ;
Talianidis, I .
EMBO JOURNAL, 2005, 24 (14) :2624-2633
[8]
The Bile Acid Receptor GPBAR-1 (TGR5) Modulates Integrity of Intestinal Barrier and Immune Response to Experimental Colitis [J].
Cipriani, Sabrina ;
Mencarelli, Andrea ;
Chini, Maria Giovanna ;
Distrutti, Eleonora ;
Renga, Barbara ;
Bifulco, Giuseppe ;
Baldelli, Franco ;
Donini, Annibale ;
Fiorucci, Stefano .
PLOS ONE, 2011, 6 (10)
[9]
FXR activation reverses insulin resistance and lipid abnormalities and protects against liver steatosis in Zucker (fa/fa) obese rats [J].
Cipriani, Sabrina ;
Mencarelli, Andrea ;
Palladino, Giuseppe ;
Fiorucci, Stefano .
JOURNAL OF LIPID RESEARCH, 2010, 51 (04) :771-784
[10]
Farnesoid X receptor agonists suppress hepatic apolipoprotein CIII expression [J].
Claudel, T ;
Inoue, Y ;
Barbier, O ;
Duran-Sandoval, D ;
Kosykh, V ;
Fruchart, J ;
Fruchart, JC ;
Gonzalez, FJ ;
Staels, B .
GASTROENTEROLOGY, 2003, 125 (02) :544-555