Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease with Fibrosis

Area of Science:

• Hepatology
• Animal Models
• Metabolic Diseases

Background:

• Liver fibrosis is a key predictor of poor outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD).
• Existing mouse models struggle to reliably induce liver fibrosis, limiting preclinical research.
• A robust animal model is crucial for understanding MASLD progression and therapeutic development.

Purpose of the Study:

• To establish and characterize a mouse model of MASLD that accurately replicates human disease features, including liver fibrosis.
• To provide a reliable platform for investigating MASLD pathophysiology and evaluating potential therapeutic interventions.

Main Methods:

• Utilized hyperphagic Ay mice fed a high-fat, high-fructose diet to mimic human dietary patterns.
• Monitored development of hepatic steatosis, injury, inflammation, and fibrosis over time (16 weeks to 12 months).
• Quantified fibrosis using histological picro-sirius red staining and hydroxyproline content analysis.

Main Results:

• The developed mouse model exhibited hepatic steatosis, injury, inflammation, and progressive fibrosis (stage 1 to stage 3).
• Mice developed associated metabolic complications: obesity, hypertriglyceridemia, glucose intolerance, and hyperinsulinemia.
• The model successfully replicated human MASLD histopathology, gene expression, and metabolic dysfunction.

Conclusions:

• This mouse model provides a valuable tool for studying the mechanisms of MASLD and its associated liver fibrosis.
• The model's ability to replicate key human disease features makes it suitable for preclinical testing of novel MASLD therapies.