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A male mouse model for metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma
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A male mouse model for metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma
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Journal Article
A male mouse model for metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma
2024
Overview
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.
Metabolic dysfunction-associated steatotic liver disease (MASLD) characterizes a spectrum of liver disorders initiated by hepatic lipid accumulation associated with metabolic syndrome. Here, the authors generate a mouse model that recapitulates the main histopathologic, transcriptomics, and metabolic alterations observed in MASLD patients.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/63
/ 38/91
/ 64/60
/ 82/51
/ Animals
/ Carcinoma, Hepatocellular - genetics
/ Carcinoma, Hepatocellular - metabolism
/ Carcinoma, Hepatocellular - pathology
/ Diabetes mellitus (non-insulin dependent)
/ Diabetes Mellitus, Type 2 - complications
/ Diabetes Mellitus, Type 2 - metabolism
/ Diet, High-Fat - adverse effects
/ Fibrosis
/ Humanities and Social Sciences
/ Humans
/ Lipids
/ Liver
/ Liver Cirrhosis - metabolism
/ Liver Neoplasms - metabolism
/ Male
/ Mice
/ Non-alcoholic Fatty Liver Disease - complications
/ Non-alcoholic Fatty Liver Disease - metabolism
/ Non-alcoholic Fatty Liver Disease - pathology
/ Science
