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An improved mouse model that rapidly develops fibrosis in non-alcoholic steatohepatitis.
Int J Exp Pathol. 2013 Apr; 94(2):93-103.IJ

Abstract

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. C57BL/6J 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, C57BL/6J mice had developed enlarged fatty liver with fibrosis as assessed by Masson'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.

Authors+Show Affiliations

Fuji-Gotemba Research Laboratories, Chugai Research Institute for Medical Science Inc, Gotemba, Shizuoka, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23305254

Citation

Matsumoto, Masahiko, et al. "An Improved Mouse Model That Rapidly Develops Fibrosis in Non-alcoholic Steatohepatitis." International Journal of Experimental Pathology, vol. 94, no. 2, 2013, pp. 93-103.
Matsumoto M, Hada N, Sakamaki Y, et al. An improved mouse model that rapidly develops fibrosis in non-alcoholic steatohepatitis. Int J Exp Pathol. 2013;94(2):93-103.
Matsumoto, M., Hada, N., Sakamaki, Y., Uno, A., Shiga, T., Tanaka, C., Ito, T., Katsume, A., & Sudoh, M. (2013). An improved mouse model that rapidly develops fibrosis in non-alcoholic steatohepatitis. International Journal of Experimental Pathology, 94(2), 93-103. https://doi.org/10.1111/iep.12008
Matsumoto M, et al. An Improved Mouse Model That Rapidly Develops Fibrosis in Non-alcoholic Steatohepatitis. Int J Exp Pathol. 2013;94(2):93-103. PubMed PMID: 23305254.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An improved mouse model that rapidly develops fibrosis in non-alcoholic steatohepatitis. AU - Matsumoto,Masahiko, AU - Hada,Natsuko, AU - Sakamaki,Yoshiyuki, AU - Uno,Akiko, AU - Shiga,Toshihiko, AU - Tanaka,Chiaki, AU - Ito,Tsuneo, AU - Katsume,Asao, AU - Sudoh,Masayuki, Y1 - 2013/01/11/ PY - 2012/05/27/received PY - 2012/10/29/accepted PY - 2013/1/12/entrez PY - 2013/1/12/pubmed PY - 2014/10/8/medline KW - fibrosis KW - high-fat diet KW - methionine-restricted diet KW - mouse model KW - non-alcoholic steatohepatitis SP - 93 EP - 103 JF - International journal of experimental pathology JO - Int J Exp Pathol VL - 94 IS - 2 N2 - 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. C57BL/6J 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, C57BL/6J mice had developed enlarged fatty liver with fibrosis as assessed by Masson'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. SN - 1365-2613 UR - https://www.unboundmedicine.com/medline/citation/23305254/An_improved_mouse_model_that_rapidly_develops_fibrosis_in_non_alcoholic_steatohepatitis_ L2 - https://doi.org/10.1111/iep.12008 DB - PRIME DP - Unbound Medicine ER -