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A researcher’s guide to preclinical mouse NASH models

Lookup NU author(s): Professor Quentin AnsteeORCiD

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Abstract

© 2022, Springer Nature Limited. Non-alcoholic fatty liver disease (NAFLD) and its inflammatory form, non-alcoholic steatohepatitis (NASH), have quickly risen to become the most prevalent chronic liver disease in the Western world and are risk factors for the development of hepatocellular carcinoma (HCC). HCC is not only one of the most common cancers but is also highly lethal. Nevertheless, there are currently no clinically approved drugs for NAFLD, and NASH-induced HCC poses a unique metabolic microenvironment that may influence responsiveness to certain treatments. Therefore, there is an urgent need to better understand the pathogenesis of this rampant disease to devise new therapies. In this line, preclinical mouse models are crucial tools to investigate mechanisms as well as novel treatment modalities during the pathogenesis of NASH and subsequent HCC in preparation for human clinical trials. Although, there are numerous genetically induced, diet-induced and toxin-induced models of NASH, not all of these models faithfully phenocopy and mirror the human pathology very well. In this Perspective, we shed some light onto the most widely used mouse models of NASH and highlight some of the key advantages and disadvantages of the various models with an emphasis on ‘Western diets’, which are increasingly recognized as some of the best models in recapitulating the human NASH pathology and comorbidities.


Publication metadata

Author(s): Gallage S, Avila JEB, Ramadori P, Focaccia E, Rahbari M, Ali A, Malek NP, Anstee QM, Heikenwalder M

Publication type: Article

Publication status: Published

Journal: Nature Metabolism

Year: 2022

Volume: 4

Pages: 1632-1649

Print publication date: 01/12/2022

Online publication date: 20/12/2022

Acceptance date: 26/10/2022

ISSN (electronic): 2522-5812

Publisher: Nature Research

URL: https://doi.org/10.1038/s42255-022-00700-y

DOI: 10.1038/s42255-022-00700-y


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