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Updated: May 7, 2026
An Advanced Murine Model for Nonalcoholic Steatohepatitis in Association with Type 2 Diabetes
Published on: April 26, 2019
A male mouse model for metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma
Byung-Kwan Jeong1,2, Won-Il Choi1,2, Wonsuk Choi3
1Graduate School of Medical Science and Engineering, KAIST, Daejeon, 34141, Korea.
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.
Insights
A new mouse model (STZ+HFD) effectively mimics metabolic dysfunction-associated steatotic liver disease (MASLD), including fatty liver, steatohepatitis (MASH), fibrosis, and cancer. This model aids in understanding MASLD and testing treatments.
Area of Science:
- Hepatology
- Metabolic Diseases
- Oncology
Background:
- Preclinical models are crucial for understanding metabolic dysfunction-associated steatotic liver disease (MASLD) and developing treatments.
- Existing models often fail to capture the full spectrum of MASLD, hindering research progress.
Purpose of the Study:
- To develop and validate a novel mouse model that recapitulates the entire MASLD spectrum.
- To utilize this model for investigating MASLD pathophysiology and evaluating therapeutic interventions.
Main Methods:
- Induction of a mouse model using Streptozotocin and a high-fat diet (STZ+HFD).
- Assessment of histopathological, transcriptomic, and metabolic changes over time.
- Evaluation of therapeutic effects of dietary modifications and tirzepatide administration.
Main Results:
- The STZ+HFD model progressively develops fatty liver, metabolic dysfunction-associated steatohepatitis (MASH), hepatic fibrosis, and hepatocellular carcinoma (HCC).
- Hepatic transcriptomic profiles in the model closely mirror those of human patients with obesity, type 2 diabetes mellitus, MASH, and MASLD-related HCC.
- Dietary interventions and tirzepatide treatment significantly ameliorated MASH, fibrosis, and tumorigenesis in the STZ+HFD mice.
Conclusions:
- A robust murine model for MASLD has been successfully established, encompassing key histopathological, transcriptomic, and metabolic features.
- This STZ+HFD model provides a valuable platform for advancing MASLD research and therapeutic development.
- The findings highlight the potential of dietary changes and specific pharmacological agents in managing MASLD progression.
