• [Nature Communications] A male mouse model for metabolic dysfunction-associated steatotic liver disease and hepatocellular carc
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  • 2024-08-19 09:22:05|
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[Title]
 A male mouse model for metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma

[Author]

Byung-Kwan Jeong 1,2,8, Won-Il Choi 1,2,8, Wonsuk Choi3,8 , Jieun Moon1,2, Won Hee Lee1,2, Chan Choi4 , In Young Choi5 , Sang-Hyun Lee5 , Jung Kuk Kim 5 , Young Seok Ju 1,2, Pilhan Kim 1,2, Young-Ah Moon6 , Jun Yong Park 7 & Hail Kim 1,2

1Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Korea.
2 Biomedical Research Center, KAIST, Daejeon, Korea.
3 Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea.
4 Department of Pathology, Chonnam National University Medical School, Hwasun, Korea.
5 Hanmi Research Center, Hanmi Pharmaceutical Co. Ltd, Hwaseong, Korea.
6 Department of Molecular Medicine, Inha University College of Medicine, Incheon 22212, Korea.
7 Department of Internal Medicine, Yonsei University College of Medicine, Yonsei Liver Center, Severance Hospital, Seoul, Korea.
8 These authors contributed equally: Byung-Kwan Jeong, Won-Il Choi, Wonsuk Choi.
e-mail: wonsuc1@uci.edu; drpjy@yuhs.ac; hailkim@kaist.edu


[Journal] 

Nature Communications volume 15, Article number: 6506 (2024)

[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.

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