Comparison of Gene Expression Patterns Between Mouse Models of Nonalcoholic Fatty Liver Disease and Liver Tissues From Patients.

Teufel, Andreas; Itzel, Timo; Erhart, Wiebke; Brosch, Mario; Wang, Xiao Yu; Kim, Yong Ook; von Schönfels, Witigo; Herrmann, Alexander; Brückner, Stefan; Stickel, Felix; Dufour, Jean-François; Chavakis, Triantafyllos; Hellerbrand, Claus; Spang, Rainer; Maass, Thorsten; Becker, Thomas; Schreiber, Stefan; Schafmayer, Clemens; Schuppan, Detlef and Hampe, Jochen (2016). Comparison of Gene Expression Patterns Between Mouse Models of Nonalcoholic Fatty Liver Disease and Liver Tissues From Patients. Gastroenterology, 151(3), pp. 513-525. Elsevier 10.1053/j.gastro.2016.05.051

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BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Mouse models of NAFLD have been used in studies of pathogenesis and treatment, and have certain features of the human disease. We performed a systematic transcriptome-wide analysis of liver tissues from patients at different stages of NAFLD progression (ranging from healthy obese individuals to those with steatosis), as well as rodent models of NAFLD, to identify those that most closely resemble human disease progression in terms of gene expression patterns. METHODS We performed a systematic evaluation of genome-wide messenger RNA expression using liver tissues collected from mice fed a standard chow diet (controls) and 9 mouse models of NAFLD: mice on a high-fat diet (with or without fructose), mice on a Western-type diet, mice on a methionine- and choline-deficient diet, mice on a high-fat diet given streptozotocin, and mice with disruption of Pten in hepatocytes. We compared gene expression patterns with those of liver tissues from 25 patients with nonalcoholic steatohepatitis (NASH), 27 patients with NAFLD, 15 healthy obese individuals, and 39 healthy nonobese individuals (controls). Liver samples were obtained from patients undergoing liver biopsy for suspected NAFLD or NASH, or during liver or bariatric surgeries. Data sets were analyzed using the limma R-package. Overlap of functional profiles was analyzed by gene set enrichment analysis profiles. RESULTS We found differences between human and mouse transcriptomes to be significantly larger than differences between disease stages or models. Of the 65 genes with significantly altered expression in patients with NASH and 177 genes with significantly altered expression in patients with NAFLD, compared with controls, only 1-18 of these genes also differed significantly in expression between mouse models of NAFLD and control mice. However, expression of genes that regulate pathways associated with the development of NAFLD were altered in some mouse models (such as pathways associated with lipid metabolism). On a pathway level, gene expression patterns in livers of mice on the high-fat diet were associated more closely with human fatty liver disease than other models. CONCLUSIONS In comparing gene expression profiles between liver tissues from different mouse models of NAFLD and patients with different stages of NAFLD, we found very little overlap. Our data set is available for studies of pathways that contribute to the development of NASH and NAFLD and selection of the most applicable mouse models (http://www.nash-profiler.com).

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

04 Faculty of Medicine > Other Institutions > Teaching Staff, Faculty of Medicine

UniBE Contributor:

Stickel, Felix and Dufour, Jean-François

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0016-5085

Publisher:

Elsevier

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

05 Apr 2017 11:35

Last Modified:

05 Apr 2017 11:35

Publisher DOI:

10.1053/j.gastro.2016.05.051

PubMed ID:

27318147

Uncontrolled Keywords:

Comparative; Cross-Species Analysis; Steatosis; Transcriptome

BORIS DOI:

10.7892/boris.93548

URI:

https://boris.unibe.ch/id/eprint/93548

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