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A male mouse model for metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma

Author

Listed:
  • Byung-Kwan Jeong

    (KAIST
    KAIST)

  • Won-Il Choi

    (KAIST
    KAIST)

  • Wonsuk Choi

    (Chonnam National University Medical School)

  • Jieun Moon

    (KAIST
    KAIST)

  • Won Hee Lee

    (KAIST
    KAIST)

  • Chan Choi

    (Chonnam National University Medical School)

  • In Young Choi

    (Hanmi Pharmaceutical Co. Ltd)

  • Sang-Hyun Lee

    (Hanmi Pharmaceutical Co. Ltd)

  • Jung Kuk Kim

    (Hanmi Pharmaceutical Co. Ltd)

  • Young Seok Ju

    (KAIST
    KAIST)

  • Pilhan Kim

    (KAIST
    KAIST)

  • Young-Ah Moon

    (Inha University College of Medicine)

  • Jun Yong Park

    (Severance Hospital)

  • Hail Kim

    (KAIST
    KAIST)

Abstract

The lack of an appropriate preclinical model of metabolic dysfunction-associated steatotic liver disease (MASLD) that recapitulates the whole disease spectrum impedes exploration of disease pathophysiology and the development of effective treatment strategies. Here, we develop a mouse model (Streptozotocin with high-fat diet, STZ + HFD) that gradually develops fatty liver, metabolic dysfunction-associated steatohepatitis (MASH), hepatic fibrosis, and hepatocellular carcinoma (HCC) in the context of metabolic dysfunction. The hepatic transcriptomic features of STZ + HFD mice closely reflect those of patients with obesity accompanying type 2 diabetes mellitus, MASH, and MASLD-related HCC. Dietary changes and tirzepatide administration alleviate MASH, hepatic fibrosis, and hepatic tumorigenesis in STZ + HFD mice. In conclusion, a murine model recapitulating the main histopathologic, transcriptomic, and metabolic alterations observed in MASLD patients is successfully established.

Suggested Citation

  • Byung-Kwan Jeong & Won-Il Choi & Wonsuk Choi & Jieun Moon & Won Hee Lee & Chan Choi & In Young Choi & Sang-Hyun Lee & Jung Kuk Kim & Young Seok Ju & Pilhan Kim & Young-Ah Moon & Jun Yong Park & Hail K, 2024. "A male mouse model for metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50660-y
    DOI: 10.1038/s41467-024-50660-y
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    References listed on IDEAS

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    1. Helen Jarvis & Dawn Craig & Robert Barker & Gemma Spiers & Daniel Stow & Quentin M Anstee & Barbara Hanratty, 2020. "Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies," PLOS Medicine, Public Library of Science, vol. 17(4), pages 1-20, April.
    2. Yujin Hoshida & Jean-Philippe Brunet & Pablo Tamayo & Todd R Golub & Jill P Mesirov, 2007. "Subclass Mapping: Identifying Common Subtypes in Independent Disease Data Sets," PLOS ONE, Public Library of Science, vol. 2(11), pages 1-8, November.
    3. Akshat Singhal & Song Cao & Christopher Churas & Dexter Pratt & Santo Fortunato & Fan Zheng & Trey Ideker, 2020. "Multiscale community detection in Cytoscape," PLOS Computational Biology, Public Library of Science, vol. 16(10), pages 1-10, October.
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