Bile Acids and Nonalcoholic Fatty Liver Disease: Molecular Insights and Therapeutic Perspectives

• Type of Material: Article
• Authors: Juan P. Arab, Pontificia Universidad Católica de Chile; Saul Karpen, Emory University; Paul Dawson, Emory University; Marco Arrese, Pontificia Universidad Católica de Chile; Michael Trauner, Medical University of Vienna
• Language: English
• Date: 2017-01-01
• Publisher: Wiley: 12 months
• Publication Version: Final Published Version
• Copyright Statement: © 2016 The Authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/hep.28709
• Title of Journal or Parent Work: Hepatology
• ISSN: 0270-9139
• Volume: 65
• Issue: 1
• Start Page: 350
• End Page: 362
• Grant/Funding Information: This work was funded, in part, by grants from the Fondo Nacional De Ciencia y Tecnología de Chile (FONDECYT #1150327; to M.A.), the Comisión Nacional de Investigación, Ciencia y Tecnología (CONICYT, basal project PFB 12/2007 CARE Chile UC). Grants F3008‐B19 and F3517‐B20 from the Austrian Science Foundation (FWF), grant LS12‐008 from the Vienna Science and Technology Fund, and grant 12040 of the Medical Scientific Fund of the Mayor of the City of Vienna (to M.T.).; Support from the NIH (DK56239 [to S.J.K.] and DK47987 [to PAD]) is also acknowledged.
• Keywords: HEPATOCELLULAR-CARCINOMA; Science & Technology; OBETICHOLIC ACID; FARNESOID X-RECEPTOR; NUCLEAR RECEPTOR; HEPATIC OVEREXPRESSION; URSODEOXYCHOLIC ACID; Gastroenterology & Hepatology; OBESE ZUCKER RAT; GUT MICROBIOTA; GLUCOSE-HOMEOSTASIS; PLACEBO-CONTROLLED TRIAL; Life Sciences & Biomedicine
• Research Categories: Health Sciences, General; Health Sciences, Medicine and Surgery

Abstract

Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases. Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide and an important risk factor for both hepatic and cardiometabolic mortality. The rapidly increasing prevalence of this disease and of its aggressive form nonalcoholic steatohepatitis (NASH) will require novel therapeutic approaches to prevent disease progression to advanced fibrosis or cirrhosis and cancer. In recent years, bile acids have emerged as relevant signaling molecules that act at both hepatic and extrahepatic tissues to regulate lipid and carbohydrate metabolic pathways as well as energy homeostasis. Activation or modulation of bile acid receptors, such as the farnesoid X receptor and TGR5, and transporters, such as the ileal apical sodium-dependent bile acid transporter, appear to affect both insulin sensitivity and NAFLD/NASH pathogenesis at multiple levels, and these approaches hold promise as novel therapies. In the present review, we summarize current available data on the relationships of bile acids to NAFLD and the potential for therapeutically targeting bile-acid-related pathways to address this growing world-wide disease. (Hepatology 2017;65:350-362).