Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2018; 24(2): 179-194
Published online Jan 14, 2018. doi: 10.3748/wjg.v24.i2.179
Metabolic and hepatic effects of liraglutide, obeticholic acid and elafibranor in diet-induced obese mouse models of biopsy-confirmed nonalcoholic steatohepatitis
Kirstine S Tølbøl, Maria NB Kristiansen, Henrik H Hansen, Sanne S Veidal, Kristoffer TG Rigbolt, Matthew P Gillum, Jacob Jelsing, Niels Vrang, Michael Feigh
Kirstine S Tølbøl, Maria NB Kristiansen, Henrik H Hansen, Sanne S Veidal, Kristoffer TG Rigbolt, Jacob Jelsing, Niels Vrang, Michael Feigh, Gubra Aps, Hørsholm DK-2970, Denmark
Kirstine S Tølbøl, Maria NB Kristiansen, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark
Kirstine S Tølbøl, Matthew P Gillum, Section for Metabolic Imaging and Liver Metabolism, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark
Niels Vrang, Department of Chemistry, Faculty of Science, University of Copenhagen, Copenhagen DK-2200, Denmark
Author contributions: Tølbøl KS and Kristiansen MNB contributed equally to the work; Jelsing J, Vrang N and Feigh M designed the study; Tølbøl KS, Kristiansen MNB, Veidal SS and Rigbolt KTG acquired and analysed data; Tølbøl KS, Kristiansen MNB, Hansen HH, Veidal SS, Rigbolt KTG, Gillum MP, Jelsing J, Vrang N and Feigh M interpreted the data and contributed to writing the article, editing and reviewing, all authors approved the final version of the article.
Supported by Innovation Fund Denmark, KST; No. 5016-00168B; and MNBK, No. 5189-00040B.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals (Licence No. 2013-15-2934-00784, The Animal Experiments Inspectorate, Denmark).
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
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: Kirstine S Tølbøl, MSc, Research Scientist, Gubra Aps, Hørsholm Kongevej 11B, Hørsholm DK-2970, Denmark. kst@gubra.dk
Telephone: +45-23-1522650
Received: September 25, 2017
Peer-review started: September 25, 2017
First decision: November 3, 2017
Revised: November 24, 2017
Accepted: December 5, 2017
Article in press: December 5, 2017
Published online: January 14, 2018
Processing time: 110 Days and 20.4 Hours
Core Tip

Core tip: The pharmacodynamics of three compounds in advanced clinical development for the treatment of nonalcoholic steatohepatitis (NASH), including liraglutide, elafibranor and obeticholic acid, were evaluated in wild-type and genetically (ob/ob) obese mouse models of NASH. Prior to treatment, all mice underwent liver biopsy for confirmation and stratification of liver steatosis and fibrosis. Within-subject comparisons were performed on changes in liver histopathology. Wild-type and ob/ob-NASH obese mice showed distinct treatment effects of liraglutide, OCA, and elafibranor, being in general agreement with corresponding findings in clinical trials for NASH. In conclusion, the two obese mouse models of NASH show clinical translatability with respect to disease etiology, histopathology and drug treatment effects, which supports their utility in preclinical drug development.