정병관 (KAIST, 현 서울아산병원 병리과)

한빛사논문

조회132

정병관Byung-Kwan Jeong

KAIST, 현 서울아산병원 병리과

Nat. Commun., Aug 02 2024, 15 (1) | https://doi.org/10.1038/s41467-024-50660-y A male mouse model for metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma

Byung-Kwan Jeong ^1,2,8, Won-Il Choi ^1,2,8, Wonsuk Choi ^3,8,*, Jieun Moon ^1,2, Won Hee Lee ^1,2, Chan Choi ⁴, In Young Choi ⁵, Sang-Hyun Lee ⁵, Jung Kuk Kim ⁵, Young Seok Ju ^1,2, Pilhan Kim ^1,2, Young-Ah Moon ⁶, Jun Yong Park ^7,*& Hail Kim^1,2,*

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

^*Corresponding authors: correspondence to Wonsuk Choi, Jun Yong Park or Hail Kim

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.

논문정보

형식Research article
게재일2024년 08월 (BRIC 등록일 2024-08-05)
연구진국내 연구진
분야 의약학 > 분자세포의학

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