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Updated: Aug 14, 2026
Incorporation of a Survivable Liver Biopsy Procedure in Mice to Assess Non-alcoholic Steatohepatitis NASH Resolution
Published on: April 16, 2019
A diet-driven metabolic dysfunction-associated steatohepatitis (MASH) mouse model resembles the corresponding human
Guilherme Ribeiro Romualdo1, Letícia C Valente2,3, Gabriel P Bacil3
1Experimental Research Unit (UNIPEX), Botucatu Medical School, São Paulo State University (UNESP), Av. Prof. Mário Rubens Guimarães Montenegro, s/n -Rubião Jr, Botucatu, SP, 18618687, Brazil. guilherme.romualdo@unesp.br.
A new mouse model accurately mimics human metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH), showing obesity, impaired glucose metabolism, and liver fibrosis. This model offers valuable insights into MASH pathogenesis and therapeutic interventions.
Area of Science:
- Hepatology
- Metabolic Diseases
- Animal Models
Background:
- Current preclinical models for metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) often lack key features like metabolic comorbidities and liver fibrosis.
- Developing a standardized and translatable MASLD/MASH model is crucial for advancing research and therapeutic development.
Purpose of the Study:
- To characterize a Western diet-induced mouse model for MASLD/MASH, evaluating its morphological, biochemical, and transcriptomic similarities to human disease.
- To establish a reliable preclinical model for studying the inflammatory and fibrosis axis in MASH.
Main Methods:
- Male C57BL/6J mice were fed a hypercaloric Western diet with high sucrose, saturated fat, cholesterol, and sugar solution for 24 weeks.
- Morphological, biochemical, and transcriptomic analyses were performed to assess MASH phenotype, including obesity, glucose metabolism, steatosis, and fibrosis.
- Computational analysis compared gene expression in the mouse model with human steatohepatitis samples.
Main Results:
- The mouse model exhibited a MASH phenotype with obesity, impaired glucose metabolism, hypercholesterolemia, extensive liver steatosis, and mild-to-moderate fibrosis.
- Significant upregulation of genes associated with inflammation (IL-6, TNF-α), collagen synthesis, cytokines, chemokines, and metalloproteinases was observed.
- Downregulated genes included negative regulators of gluconeogenesis, insulin secretion, and lipid biosynthesis, notably the major urinary protein (MUP) family.
- Gene expression patterns in the mouse model showed strong correlation with human steatohepatitis, particularly for fibrosis- and inflammation-related genes.
Conclusions:
- The developed Western diet-induced mouse model serves as a robust and translatable bioassay for MASH.
- This model accurately recapitulates key features of human MASH, including metabolic dysfunction and liver fibrosis.
- It provides a valuable platform for investigating the pathogenesis of MASH and for preclinical testing of therapeutic interventions targeting the inflammation-fibrosis axis.
