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

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

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...

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Main Authors: 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 Kim
Format: Article
Language:English
Published: Nature Portfolio 2024-08-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-50660-y
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Summary: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.
ISSN:2041-1723

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