Zheng, Q.; Kawaguchi, M.; Mikami, H.; Diao, P.; Zhang, X.; Zhang, Z.; Nakajima, T.; Iwadare, T.; Kimura, T.; Nakayama, J.; Tanaka, N. Establishment of Novel Mouse Model of Dietary NASH Rapidly Progressing into Liver Cirrhosis and Tumors. Cancers2023, 15, 3744.
Zheng, Q.; Kawaguchi, M.; Mikami, H.; Diao, P.; Zhang, X.; Zhang, Z.; Nakajima, T.; Iwadare, T.; Kimura, T.; Nakayama, J.; Tanaka, N. Establishment of Novel Mouse Model of Dietary NASH Rapidly Progressing into Liver Cirrhosis and Tumors. Cancers 2023, 15, 3744.
Zheng, Q.; Kawaguchi, M.; Mikami, H.; Diao, P.; Zhang, X.; Zhang, Z.; Nakajima, T.; Iwadare, T.; Kimura, T.; Nakayama, J.; Tanaka, N. Establishment of Novel Mouse Model of Dietary NASH Rapidly Progressing into Liver Cirrhosis and Tumors. Cancers2023, 15, 3744.
Zheng, Q.; Kawaguchi, M.; Mikami, H.; Diao, P.; Zhang, X.; Zhang, Z.; Nakajima, T.; Iwadare, T.; Kimura, T.; Nakayama, J.; Tanaka, N. Establishment of Novel Mouse Model of Dietary NASH Rapidly Progressing into Liver Cirrhosis and Tumors. Cancers 2023, 15, 3744.
Abstract
Non-alcoholic steatohepatitis (NASH), which is the most severe manifestation of non-alcoholic fatty liver disease (NAFLD), has been recognized as a major hepatocellular carcinoma (HCC) catalyst. However, the molecular mechanism of NAFLD-NASH-HCC sequence remains unclear and a specific and effective treatment for NASH has not yet been established. The progress in this field depends on the availability of reliable preclinical models which show the steady progress to NASH, liver cirrhosis, and HCC. However, most of NASH mouse models that have been described to date develop NASH generally for more than 24 weeks and there is an uncertainty of HCC development. To overcome such shortcomings of experimental NASH studies, we established a novel NASH-HCC mouse model with very high reproducibility, generality, and convenience. We treated male C57BL/6J mice with a newly developed choline-deficient and methionine-restricted high-fat diet (CDMRHFD) for 60 weeks. Treatment of CDMRHFD for 3 weeks revealed marked steatosis, lobular inflammation, and fibrosis, histologically diagnosed as NASH. Liver cirrhosis was observed in all mice with 36-week treatment. Liver nodule emerged at 12 weeks of the treatment, and diameter >2 mm liver tumors developed in all mice at 24 weeks of the treatment. In conclusion, our rapidly progressive and highly reproducible NASH-liver cirrhosis-HCC model is helpful for preclinical development and research on the pathogenesis of human NAFLD-NASH-HCC. Our mouse model would be useful for the development of novel chemistry for NASH-HCC-targeted therapies or HCC prevention strategies.
Medicine and Pharmacology, Gastroenterology and Hepatology
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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