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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 8, 2015; 7(28): 2811-2818
Published online Dec 8, 2015. doi: 10.4254/wjh.v7.i28.2811
Bile acid receptors and nonalcoholic fatty liver disease
Liyun Yuan, Kiran Bambha
Liyun Yuan, Department of Gastroenterology and Liver Diseases, Keck USC School of Medicine, University of Southern California, Los Angeles, CA 90033, United States
Kiran Bambha, Division of Gastroenterology and Hepatology, University of Colorado, Aurora, CO 80045, United States
Author contributions: Yuan L performed the literature search and initial publication review, drafted the manuscript, and gave final approval of the version of the article to be submitted; Bambha K developed the concept for the manuscript, performed a literature search and publication review, critically revised the manuscript, and gave final approval of the version of the article to be submitted.
Conflict-of-interest statement: The authors have no conflicts of interest regarding this manuscript submission to report.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Kiran Bambha, MD, MSc, Assistant Professor of Medicine, Division of Gastroenterology and Hepatology, University of Colorado, Anschutz Medical Campus, 12631 E. 17th Avenue, MS B-158, Aurora, CO 80045, United States. kiran.bambha@ucdenver.edu
Telephone: +1-303-7241857 Fax: +1-303-7241891
Received: July 14, 2015
Peer-review started: July 17, 2015
First decision: September 2, 2015
Revised: November 5, 2015
Accepted: November 17, 2015
Article in press: November 25, 2015
Published online: December 8, 2015
Processing time: 143 Days and 12.1 Hours
Abstract

With the high prevalence of obesity, diabetes, and other features of the metabolic syndrome in United States, nonalcoholic fatty liver disease (NAFLD) has inevitably become a very prevalent chronic liver disease and is now emerging as one of the leading indications for liver transplantation. Insulin resistance and derangement of lipid metabolism, accompanied by activation of the pro-inflammatory response and fibrogenesis, are essential pathways in the development of the more clinically significant form of NAFLD, known as nonalcoholic steatohepatitis (NASH). Recent advances in the functional characterization of bile acid receptors, such as farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor (TGR) 5, have provided further insight in the pathophysiology of NASH and have led to the development of potential therapeutic targets for NAFLD and NASH. Beyond maintaining bile acid metabolism, FXR and TGR5 also regulate lipid metabolism, maintain glucose homeostasis, increase energy expenditure, and ameliorate hepatic inflammation. These intriguing features have been exploited to develop bile acid analogues to target pathways in NAFLD and NASH pathogenesis. This review provides a brief overview of the pathogenesis of NAFLD and NASH, and then delves into the biological functions of bile acid receptors, particularly with respect to NASH pathogenesis, with a description of the associated experimental data, and, finally, we discuss the prospects of bile acid analogues in the treatment of NAFLD and NASH.

Keywords: Bile acids; Bile acid receptors; Nonalcoholic steatohepatitis; Farnesoid X receptor; Transmembrane G protein-coupled receptor 5; Nonalcoholic fatty liver disease; Hepatic steatosis

Core tip: Bile acids and bile acid receptors play important roles in modulation of feature of the metabolic syndrome, hepatic steatosis, and hepatic inflammation. Development of bile acid analogues specifically targeting farnesoid X receptor and transmembrane G protein-coupled receptor 5 provide potential novel classes of drugs for the treatment of nonalcoholic steatohepatitis.