An improved mouse model that rapidly develops fibrosis in non‐alcoholic steatohepatitis
Open accessAbstract
Summary: Non‐alcoholic steatohepatitis ( NASH ) is a progressive fibrotic disease, the pathogenesis of which has not been fully elucidated. One of the most common models used in NASH research is a nutritional model where NASH is induced by feeding a diet deficient in both methionine and choline. However, the dietary methionine‐/choline‐deficient model in mice can cause severe weight loss and liver atrophy, which are not characteristics of NASH seen in human patients. Exclusive, long‐term feeding with a high‐fat diet ( HFD ) produced fatty liver and obesity in mice, but the HFD for several months did not affect fibrosis. We aimed to establish a mouse model of NASH with fibrosis by optimizing the methionine content in the HFD . Male mice were fed a choline‐deficient, L ‐amino acid‐defined, high‐fat diet ( CDAHFD ) consisting of 60 kcal% fat and 0.1% methionine by weight. After 1–14 weeks of being fed CDAHFD , the mice were killed. C 57 BL /6 J mice maintained or gained weight when fed CDAHFD , while A/J mice showed a steady decline in body weight (of up to 20% of initial weight). In both strains of mice, plasma levels of alanine aminotransferase increased from week 1, when hepatic steatosis was also observed. By week 6, C 57 BL /6 J mice had developed enlarged fatty liver with fibrosis as assessed by M asson's trichrome staining and by hydroxyproline assay. Therefore, this improved CDAHFD model may be a mouse model of rapidly progressive liver fibrosis and be potentially useful for better understanding human NASH disease and in the development of efficient therapies for this condition.
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The CDAHFD mouse diet produces rapid steatosis, inflammation, and fibrosis.
“The CDAHFD, which combines choline deprivation with a high-fat content and defined amino acid composition, elicits rapid-onset steatosis, inflammation, and fibrosis (20).”
From Regulatory T cells safeguard liver health during metabolic-associated steatohepatitis (2026) · cites this paper as [20]
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“The CDAHFD, which combines choline deprivation with a high - fat content and defined amino acid composition, elicits rapid - onset steatosis, inflammation, and fibrosis (20).”
- Authors
- Matsumoto, M., Hada, N., Sakamaki, Y., Uno, A., Shiga, T., Tanaka, C., Ito, T., Katsume, A., & Sudoh, M.
- Affiliations
- Chugai Research Institute For Medical Science, Inc. (Japan) (JP)
- Chugai Pharmaceutical Co., Ltd. (Japan) (JP)
- Corresponding author
- Matsumoto, Masahiko
- Venue
- International Journal of Experimental Pathology
- Publisher
- Wiley
- Published
- 2013-01-11
- Volume
- 94
- Issue
- 2
- Pages
- 93-103
- ISSN
- 0959-9673 (ISSN-L)
- 1365-2613
- PMC
- PMC3607137
- OpenAlex
- W2022273281
- Cited by
- 523
- References
- 46
- Citations by year
- 2026: 60 · 2025: 57 · 2024: 69 · 2023: 70 · 2022: 66 · 2021: 52 · 2020: 53 · 2019: 29 · 2018: 30 · 2017: 17 · 2016: 9 · 2015: 5 · 2014: 3 · 2013: 1
- FWCI
- 4.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Experimental Pathology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chugai Pharmaceutical
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- nonalcoholic steatohepatitis, liver fibrosis, mouse model, choline-deficient diet, high-fat diet, hepatic steatosis, alanine aminotransferase, C57BL/6J mice, A/J mice, weight loss, hydroxyproline
- MeSH terms
- Alanine Transaminase, Animals, Aspartate Aminotransferases, Choline Deficiency, Disease Models, Animal, Fatty Liver, Humans, Liver, Liver Cirrhosis, Male, Methionine, Mice, Inbred A, Mice, Inbred C57BL, Obesity, Specific Pathogen-Free Organisms, Time Factors, Biomarkers, Diet, Fat-Restricted, Mice, Diet, High-Fat, Non-alcoholic Fatty Liver Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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