Animal Models of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of hepatic disorders characterised initially by simple lipid accumulation (steatosis) and potentially progressing to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma. Animal models have been indispensable for elucidating pathogenic mechanisms, validating biomarkers and testing therapeutic interventions. Dietary models—such as high-fat, high-fructose or methionine–choline-deficient regimens—mimic nutritional drivers of human disease, while genetically modified rodents (for example ob/ob and db/db mice or apolipoprotein-E-deficient strains) reveal the contribution of specific metabolic or inflammatory pathways. Combination approaches, integrating dietary stressors with low-dose hepatotoxins, can accelerate fibrogenesis and tumourigenesis, recapitulating later stages of human NAFLD. Precise choice of model depends on the stage of disease under investigation: early-phase lipid handling, immune-mediated injury, hepatic stellate cell activation or malignant transformation. Despite ongoing refinements, no single model fully captures the clinical heterogeneity of human NAFLD, underscoring the importance of complementary systems and standardised protocols to ensure reproducibility and translational relevance.

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Animal Models of Nonalcoholic Fatty Liver Disease publication trend

The graph below shows the total number of articles in animal models of nonalcoholic fatty liver disease across all publications each year (not limited to Nature Index journals).

Technical terms

Nonalcoholic fatty liver disease (NAFLD): A spectrum of liver disorders arising from fat accumulation in the absence of significant alcohol intake.

Nonalcoholic steatohepatitis (NASH): A progressive form of NAFLD characterised by hepatocellular injury, inflammation and variable fibrosis.

Steatosis: The accumulation of triglycerides within hepatocytes, marking the earliest stage of NAFLD.

Fibrosis: Deposition of extracellular matrix components by activated stellate cells, leading to scarring and impaired liver function.

Hepatocellular carcinoma (HCC): A primary malignant tumour of the liver that can arise from advanced NASH and cirrhosis.

Methionine–choline-deficient (MCD) diet: A nutritional regimen lacking key methyl donors, often used to induce steatohepatitis and fibrosis rapidly in rodents.

High-fat, high-fructose diet: A nutritional model combining elevated fat and sugar to mimic Western-style eating and drive metabolic features of human NAFLD.

References

1. Phenotypic and metabolomic characteristics of mouse models of metabolic associated steatohepatitis. Biomarker Research (2024).
2. The genetic background shapes the susceptibility to mitochondrial dysfunction and NASH progression. Journal of Experimental Medicine (2023).
3. Animal Models of Nonalcoholic Fatty Liver Disease—A Starter’s Guide. Nutrients (2017).
4. A Systematic Review of Animal Models of NAFLD Finds High‐Fat, High‐Fructose Diets Most Closely Resemble Human NAFLD. Hepatology (2021).