ArticleAlcoholism, clinical and experimental research2021
A Western diet with alcohol in drinking water recapitulates features of alcohol-associated liver disease in mice.
Article in Alcoholism, clinical and experimental research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Ethanol reshapes FFC-driven steatohepatitis through time-dependent fibrosis and lipid-droplet remodeling.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Precision pathophysiology in steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Therapeutics for Alcohol-Associated Liver Disease.Annual review of pharmacology and toxicology · 2026Review
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- Article
- Timing matters: circadian rhythm disruption in alcohol-associated peripheral organ pathophysiology.Function (Oxford, England) · 2026Review
- Lipid Droplet Dynamics in Alcoholic Steatohepatitis.The American journal of pathology · 2026Review
- An Update on Animal Models of Alcohol-Associated Liver Disease.The American journal of pathology · 2026Review
- Beyond diabetes and obesity: GLP-1 receptor agonists as multifunctional therapeutics across the steatotic liver disease spectrum.Frontiers in pharmacology · 2026Review
- Identification of Preclinical Biomarkers of Metabolic Dysfunction-Associated Steatotic Liver Disease versus Metabolic Dysfunction and Alcohol-Associated Liver Disease and the Impact of Diet.The American journal of pathology · 2026Article
- Liver Macrophage Changes during Early Adaptation to Alcohol Exposure.The American journal of pathology · 2026Article
- Alcohol and Metabolic Stress Synergize to Dysregulate Mitochondrial Health and Lipid Metabolism; Evidence from a Hepatocyte Spheroid Model.Function (Oxford, England) · 2025Article
- Alcohol-induced KDM5B activation in hepatocytes drives pathogenic cell-cell communication, leading to loss of liver function.Hepatology communications · 2025Article
- Metabolic dysfunction and alcohol-associated liver disease (MetALD).eGastroenterology · 2025Review
- Sensitive Profiling of Mouse Liver Membrane Proteome Dysregulation Following a High-Fat and Alcohol Diet Treatment.Proteomics · 2024Article
- Emerging concepts in alcohol, infection & immunity: A summary of the 2023 alcohol and immunology research interest group (AIRIG) meeting.Alcohol (Fayetteville, N.Y.) · 2024Article
- A novel experimental model of MetALD in male mice recapitulates key features of severe alcohol-associated hepatitis.Hepatology communications · 2024Article
- Protective role of 17β-estradiol in alcohol-associated liver fibrosis is mediated by suppression of integrin signaling.Hepatology communications · 2024Article
- Alcohol-associated liver disease.The Journal of clinical investigation · 2024Review
- New murine model of alcoholic hepatitis in obesity-induced metabolic-associated fatty liver disease.Experimental animals · 2023Article
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Authors and funding
8 authors at 1 institution in 1 country.
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Abstract
backgroundMouse models of alcohol-associated liver disease vary greatly in their ease of implementation and the pathology they produce. Effects range from steatosis and mild inflammation with the Lieber-DeCarli liquid diet to severe inflammation, fibrosis, and pyroptosis seen with the Tsukamoto-French intragastric feeding model. Implementation of all of these models is limited by the labor-intensive nature of the protocols and the specialized skills necessary for successful intragastric feeding. We thus sought to develop a new model to reproduce features of alcohol-induced inflammation and fibrosis with minimal operational requirements.
methodsOver a 16-week period, mice were fed ad libitum with a pelleted high-fat Western diet (WD; 40% calories from fat) and alcohol added to the drinking water. We found the optimal alcohol consumption to be that at which the alcohol concentration was 20% for 4 days and 10% for 3 days per week. Control mice received WD pellets with water alone.
resultsAlcohol consumption was 18 to 20 g/kg/day in males and 20 to 22 g/kg/day in females. Mice in the alcohol groups developed elevated serum transaminase levels after 12 weeks in males and 10 weeks in females. At 16 weeks, both males and females developed liver inflammation, steatosis, and pericellular fibrosis. Control mice on WD without alcohol had mild steatosis only. Alcohol-fed mice showed reduced HNF4α mRNA and protein expression. HNF4α is a master regulator of hepatocyte differentiation, down-regulation of which is a known driver of hepatocellular failure in alcoholic hepatitis.
conclusionA simple-to-administer, 16-week WD alcohol model recapitulates the inflammatory, fibrotic, and gene expression aspects of human alcohol-associated steatohepatitis.
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