Cargando…

Mouse model of NASH that replicates key features of the human disease and progresses to fibrosis stage 3

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States and the world; with no Food and Drug Administration–approved pharmacological treatment available, it remains an area of unmet medical need. In nonalcoholic steatohepatitis (NASH), the most important predic...

Descripción completa

Detalles Bibliográficos
Autores principales: St. Rose, Kristy, Yan, Jun, Xu, Fangxi, Williams, Jasmine, Dweck, Virginia, Saxena, Deepak, Schwabe, Robert F., Caviglia, Jorge Matias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9512466/
https://www.ncbi.nlm.nih.gov/pubmed/35923109
http://dx.doi.org/10.1002/hep4.2035
_version_ 1784797844762263552
author St. Rose, Kristy
Yan, Jun
Xu, Fangxi
Williams, Jasmine
Dweck, Virginia
Saxena, Deepak
Schwabe, Robert F.
Caviglia, Jorge Matias
author_facet St. Rose, Kristy
Yan, Jun
Xu, Fangxi
Williams, Jasmine
Dweck, Virginia
Saxena, Deepak
Schwabe, Robert F.
Caviglia, Jorge Matias
author_sort St. Rose, Kristy
collection PubMed
description Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States and the world; with no Food and Drug Administration–approved pharmacological treatment available, it remains an area of unmet medical need. In nonalcoholic steatohepatitis (NASH), the most important predictor of clinical outcome is the fibrosis stage. Moreover, the Food and Drug Administration recommends that clinical trials for drugs to treat this disease include patients with fibrosis stage 2 or greater. Therefore, when using animal models for investigating the pathophysiology of NAFLD and for the preclinical evaluation of new drugs, it is important that the animals develop substantial fibrosis. The aim of this study was to develop a mouse model of NAFLD that replicated the disease in humans, including obesity and progressive liver fibrosis. Agouti yellow mutant mice, which have hyperphagia, were fed a Western diet and water containing high‐fructose corn syrup for 16 weeks. Mice became obese and developed glucose intolerance. Their gut microbiota showed dysbiosis with changes that replicate some of the changes described in humans with NASH. They developed NASH with activity scores of 5–6 and fibrosis, which was stage 1 after 16 weeks, and stage 3 after 12 months. Changes in liver gene expression assessed by gene‐set enrichment analysis showed 90% similarity with changes in human patients with NASH. Conclusion: Ay mice, when fed a Western diet similar to that consumed by humans, develop obesity and NASH with liver histology, including fibrosis, and gene expression changes that are highly similar to the disease in humans.
format Online
Article
Text
id pubmed-9512466
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-95124662022-09-30 Mouse model of NASH that replicates key features of the human disease and progresses to fibrosis stage 3 St. Rose, Kristy Yan, Jun Xu, Fangxi Williams, Jasmine Dweck, Virginia Saxena, Deepak Schwabe, Robert F. Caviglia, Jorge Matias Hepatol Commun Original Articles Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States and the world; with no Food and Drug Administration–approved pharmacological treatment available, it remains an area of unmet medical need. In nonalcoholic steatohepatitis (NASH), the most important predictor of clinical outcome is the fibrosis stage. Moreover, the Food and Drug Administration recommends that clinical trials for drugs to treat this disease include patients with fibrosis stage 2 or greater. Therefore, when using animal models for investigating the pathophysiology of NAFLD and for the preclinical evaluation of new drugs, it is important that the animals develop substantial fibrosis. The aim of this study was to develop a mouse model of NAFLD that replicated the disease in humans, including obesity and progressive liver fibrosis. Agouti yellow mutant mice, which have hyperphagia, were fed a Western diet and water containing high‐fructose corn syrup for 16 weeks. Mice became obese and developed glucose intolerance. Their gut microbiota showed dysbiosis with changes that replicate some of the changes described in humans with NASH. They developed NASH with activity scores of 5–6 and fibrosis, which was stage 1 after 16 weeks, and stage 3 after 12 months. Changes in liver gene expression assessed by gene‐set enrichment analysis showed 90% similarity with changes in human patients with NASH. Conclusion: Ay mice, when fed a Western diet similar to that consumed by humans, develop obesity and NASH with liver histology, including fibrosis, and gene expression changes that are highly similar to the disease in humans. John Wiley and Sons Inc. 2022-08-03 /pmc/articles/PMC9512466/ /pubmed/35923109 http://dx.doi.org/10.1002/hep4.2035 Text en © 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
St. Rose, Kristy
Yan, Jun
Xu, Fangxi
Williams, Jasmine
Dweck, Virginia
Saxena, Deepak
Schwabe, Robert F.
Caviglia, Jorge Matias
Mouse model of NASH that replicates key features of the human disease and progresses to fibrosis stage 3
title Mouse model of NASH that replicates key features of the human disease and progresses to fibrosis stage 3
title_full Mouse model of NASH that replicates key features of the human disease and progresses to fibrosis stage 3
title_fullStr Mouse model of NASH that replicates key features of the human disease and progresses to fibrosis stage 3
title_full_unstemmed Mouse model of NASH that replicates key features of the human disease and progresses to fibrosis stage 3
title_short Mouse model of NASH that replicates key features of the human disease and progresses to fibrosis stage 3
title_sort mouse model of nash that replicates key features of the human disease and progresses to fibrosis stage 3
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9512466/
https://www.ncbi.nlm.nih.gov/pubmed/35923109
http://dx.doi.org/10.1002/hep4.2035
work_keys_str_mv AT strosekristy mousemodelofnashthatreplicateskeyfeaturesofthehumandiseaseandprogressestofibrosisstage3
AT yanjun mousemodelofnashthatreplicateskeyfeaturesofthehumandiseaseandprogressestofibrosisstage3
AT xufangxi mousemodelofnashthatreplicateskeyfeaturesofthehumandiseaseandprogressestofibrosisstage3
AT williamsjasmine mousemodelofnashthatreplicateskeyfeaturesofthehumandiseaseandprogressestofibrosisstage3
AT dweckvirginia mousemodelofnashthatreplicateskeyfeaturesofthehumandiseaseandprogressestofibrosisstage3
AT saxenadeepak mousemodelofnashthatreplicateskeyfeaturesofthehumandiseaseandprogressestofibrosisstage3
AT schwaberobertf mousemodelofnashthatreplicateskeyfeaturesofthehumandiseaseandprogressestofibrosisstage3
AT cavigliajorgematias mousemodelofnashthatreplicateskeyfeaturesofthehumandiseaseandprogressestofibrosisstage3