Animal models to study bile acid metabolism

• Type of Material: Article
• Authors: Jianing Li, Emory University; Paul Dawson, Emory University
• Language: English
• Date: 2019-05-01
• Publisher: ELSEVIER SCIENCE BV
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Elsevier B.V.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbadis.2018.05.011
• Title of Journal or Parent Work: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
• Volume: 1865
• Issue: 5
• Start Page: 895
• End Page: 911
• Grant/Funding Information: This work was supported by the National Institutes of Health [DK047987].
• Keywords: Intestine; Biophysics; FARNESOID X RECEPTOR; Mouse model; Cell Biology; Liver; INTESTINAL CHOLESTEROL ABSORPTION; BETA-MURICHOLIC ACID; Transporter; Enzyme; Life Sciences & Biomedicine; INDUCED LIVER-INJURY; ANION-TRANSPORTING POLYPEPTIDES; ALPHA-OST-BETA; BILIARY LIPID SECRETION; Biochemistry & Molecular Biology; Science & Technology; MDR2 P-GLYCOPROTEIN; OXYSTEROL 7-ALPHA-HYDROXYLASE GENE; Enterohepatic circulation; FAMILIAL INTRAHEPATIC CHOLESTASIS
• Research Categories: Biology, Cell; Biophysics, Medical

Abstract

The use of animal models, particularly genetically modified mice, continues to play a critical role in studying the relationship between bile acid metabolism and human liver disease. Over the past 20 years, these studies have been instrumental in elucidating the major pathways responsible for bile acid biosynthesis and enterohepatic cycling, and the molecular mechanisms regulating those pathways. This work also revealed bile acid differences between species, particularly in the composition, physicochemical properties, and signaling potential of the bile acid pool. These species differences may limit the ability to translate findings regarding bile acid-related disease processes from mice to humans. In this review, we focus primarily on mouse models and also briefly discuss dietary or surgical models commonly used to study the basic mechanisms underlying bile acid metabolism. Important phenotypic species differences in bile acid metabolism between mice and humans are highlighted.