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Updated: Aug 23, 2025
Inducing and Characterizing Vesicular Steatosis in Differentiated HepaRG Cells
Published on: July 18, 2019
Mouse models of nonalcoholic steatohepatitis and their application to new drug development
Hieu Huy Phung1, Chang Hoon Lee2
1BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Goyang, 10326, Korea.
Abstract:
Nonalcoholic steatohepatitis (NASH) is one of the important liver diseases currently attracting attention in liver research and drug development. Appropriate mouse models should be used to identify the mechanisms underlying the pathogenesis and progression of NASH in humans and to evaluate the efficacy of anti-NASH agents under development to treat this disease. In this review, we first summarised recent histopathology and pathogenesis of NASH in humans, including the concept of resolution of inflammation. We also examined whether these characteristics of NASH in humans are adequately reflected in mouse models. Through this review, we identified the usefulness and limitations of mouse models widely used in research on NASH. Mouse models can be divided into three main types: diet models, chemical models using toxic compounds, and genetic models using genetically transgenic mice. Genotype models are likely suitable for evaluating anti-NASH compounds because fibrosis, which is considered an important index to determine the drug efficacy of NASH inhibitors, is rapidly induced in genetic models. Using these models, we introduced some selected cases of NASH inhibitor development. This review aims to enhance the understanding of the pathogenesis of NASH and provide a basis for successfully selecting and utilising appropriate animal models of NASH in the development of effective inhibitors.
Insights
Selecting appropriate mouse models is crucial for understanding nonalcoholic steatohepatitis (NASH) and developing effective treatments. Genetic models show promise for evaluating anti-NASH compounds due to rapid fibrosis induction.
Area of Science:
- Hepatology
- Drug Development
- Animal Models
Background:
- Nonalcoholic steatohepatitis (NASH) is a significant liver disease with increasing research and drug development focus.
- Understanding NASH pathogenesis and progression in humans is vital for effective treatment strategies.
- Current research relies on animal models to study NASH mechanisms and test potential therapies.
Purpose of the Study:
- To review the histopathology and pathogenesis of human NASH, including inflammation resolution.
- To assess the suitability of current mouse models in reflecting human NASH characteristics.
- To identify the utility and limitations of various mouse models for NASH research and drug development.
Main Methods:
- Review of existing literature on NASH histopathology and pathogenesis in humans.
- Examination of commonly used mouse models: diet-induced, chemical-induced, and genetic models.
- Analysis of how well these models recapitulate human NASH features, particularly fibrosis.
Main Results:
- Mouse models vary in their ability to reflect human NASH complexity.
- Genetic models demonstrate rapid induction of fibrosis, a key marker for evaluating NASH inhibitor efficacy.
- Diet and chemical models have specific applications but may not fully capture all aspects of human NASH.
Conclusions:
- Appropriate selection of mouse models is critical for advancing NASH research and drug discovery.
- Genetic models are particularly valuable for preclinical evaluation of anti-NASH agents targeting fibrosis.
- Further refinement and validation of animal models are needed to accurately predict human NASH treatment outcomes.
