ArticleHepatology communications2024
A novel experimental model of MetALD in male mice recapitulates key features of severe alcohol-associated hepatitis.
Article in Hepatology communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- The global burden of metabolic and alcohol-associated liver disease (MetALD).Hepatology communications · 2026Review
- Ethanol reshapes FFC-driven steatohepatitis through time-dependent fibrosis and lipid-droplet remodeling.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- THBS1+ macrophages fuel pathogenic inflammation in alcohol-associated liver disease.Hepatology communications · 2026Article
- Precision pathophysiology in steatotic liver disease.Clinical and molecular hepatology · 2026Review
- MetALD Molecular Signatures: What We Know, What We Lack, and How to Move Forward Through Integrated Multi-Omics.Metabolites · 2026Review
- Therapeutics for Alcohol-Associated Liver Disease.Annual review of pharmacology and toxicology · 2026Review
- Article
- The versatile interplay between steatotic liver disease and liver cancer.Nature reviews. Cancer · 2026Review
- The impact of a Western diet and binge drinking on metabolic dysfunction-associated steatotic liver disease in male and female mice.Experimental physiology · 2026Article
- Beyond diabetes and obesity: GLP-1 receptor agonists as multifunctional therapeutics across the steatotic liver disease spectrum.Frontiers in pharmacology · 2026Review
- An Update on Animal Models of Alcohol-Associated Liver Disease.The American journal of pathology · 2026Review
- A combination of ethanol and arachidonic acid promotes steatosis and endoplasmic reticulum stress and impairs mitochondrial respiration in H9c2 cardiomyoblasts.Lipids in health and disease · 2025Article
- Effects of Chronic Moderate Alcohol Intake on Metabolic Phenotypes and Gut Microbiota in Lean and Obese Mice with Distinct Dietary Structures.Nutrients · 2025Article
- Alcohol and Metabolic Stress Synergize to Dysregulate Mitochondrial Health and Lipid Metabolism; Evidence from a Hepatocyte Spheroid Model.Function (Oxford, England) · 2025Article
- Physiological Mechanisms Vulnerable to Alcohol-Induced Alterations: Role in Chronic Comorbidities.Comprehensive Physiology · 2025Review
- Inflammation in MASLD progression and cancer.JHEP reports : innovation in hepatology · 2025Review
- Alcohol Consumption and Liver Metabolism in the Era of MASLD: Integrating Nutritional and Pathophysiological Insights.Nutrients · 2025Review
- New Insights into the Interplay Between Simple Sugars and Liver Diseases.Current issues in molecular biology · 2025Review
- Metabolic dysfunction and alcohol-associated liver disease (MetALD).eGastroenterology · 2025Review
- Short-term high-fat diet feeding plus acute ethanol binge induced acute liver injury in mice via oxidative stress, inflammation and pyroptosis.Frontiers in pharmacology · 2025Article
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8 authors.
Funding
Abstract
backgroundThe recent increase in the incidence of alcohol-associated hepatitis (AH) coincides with the obesity epidemic in the United States. However, current mouse models do not fully replicate the combined insults of obesity, metabolic dysfunction-associated steatohepatitis, and alcohol. The aim of this study was to develop a new mouse model that recapitulates the robust inflammatory and fibrotic phenotype characteristic of human MetALD.
methodsEight- to 10-week-old male C57BL/6 mice were fed chow or high fat-cholesterol-sugar diet (metabolic dysfunction-associated steatohepatitis diet) and in each group, some received alcohol in drinking water (ad libitum) and weekly alcohol binges (EtOH) for 3 months. The liver was assessed for features of AH.
resultsMetALD mice displayed increased liver damage indicated by highly elevated ALT and bilirubin levels compared to all other groups. Liver steatosis was significantly greater in the MetALD mice compared to all other experimental groups. The inflammatory phenotype of MetALD was also recapitulated, including increased IL-6 and IL-1β protein levels as well as increased CD68+ macrophages and Ly6G+ neutrophils in the liver. Sirius red staining and expression of collagen 1, alpha-smooth muscle actin indicated advanced fibrosis in the livers of MetALD mice. In addition, indicators of epithelial-to-mesenchymal transition markers were increased in MetALD mice compared to all other groups. Furthermore, we found increased ductular reaction, dysregulated hedgehog signaling, and decreased liver synthetic functions, consistent with severe AH.
conclusionsAlcohol administration in mice combined with metabolic dysfunction-associated steatohepatitis diet recapitulates key characteristics of human AH including liver damage, steatosis, robust systemic inflammation, and liver immune cell infiltration. This model results in advanced liver fibrosis, ductular reaction, decreased synthetic function, and hepatocyte dedifferentiation, suggesting a robust model of MetALD in mice.
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