ISSN |
1007-9327 (print) and 2219-2840 (online) |
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/ |
Copyright |
© The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved. |
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Permissions |
For details, please visit: http://www.wjgnet.com/bpg/gerinfo/207
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Publisher |
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA |
Website |
http://www.wjgnet.com |
Category |
Medicine, Research & Experimental |
Manuscript Type |
Basic Study |
Article Title |
Metabolic and hepatic effects of liraglutide, obeticholic acid and elafibranor in diet-induced obese mouse models of biopsy-confirmed nonalcoholic steatohepatitis
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Manuscript Source |
Unsolicited Manuscript |
All Author List |
Kirstine Sloth Tølbøl, Maria NB Kristiansen, Henrik H Hansen, Sanne S Veidal, Kristoffer T G Rigbolt, Matthew P Gillum, Jacob Jelsing, Niels Vrang and Michael Feigh |
ORCID |
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Funding Agency and Grant Number |
Funding Agency |
Grant Number |
Innovation Fund Denmark |
5016-00168B |
Innovation Fund Denmark |
5189-00040B |
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Corresponding Author |
Kirstine Sloth Tølbøl, MSc, Research Scientist, Pharmacology research, Gubra Aps, Hørsholm Kongevej 11b, Hørsholm 2970, Denmark. kst@gubra.dk |
Key Words |
Nonalcoholic steatohepatitis; Disease models; Pathology; Fibrosis; Liver biopsy; Transcriptomics; Pharmacodynamics; Glucagon-like peptide-1 receptor; Peroxisome proliferator-activated receptor; Farnesoid X receptor |
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. |
Publish Date |
2018-01-14 05:07 |
Citation |
Tølbøl KS, Kristiansen MNB, Hansen HH, Veidal SS, Rigbolt KTG, Gillum MP, Jelsing J, Vrang N, Feigh M. Metabolic and hepatic effects of liraglutide, obeticholic acid and elafibranor in diet-induced obese mouse models of biopsy-confirmed nonalcoholic steatohepatitis. World J Gastroenterol 2018; 24(2): 179-194 |
URL |
http://www.wjgnet.com/1007-9327/full/v24/i2/179.htm |
DOI |
http://dx.doi.org/10.3748/wjg.v24.i2.179 |