Metabolic Disorders and Animal Models in Hepatic Health

Metabolic disorders such as obesity, insulin resistance and dyslipidaemia underpin the global rise of non-alcoholic fatty liver disease (NAFLD) and its inflammatory sequel, non-alcoholic steatohepatitis (NASH). Progression from simple steatosis to hepatocyte injury, cellular ballooning and fibrotic scarring drives significant morbidity and predisposes to cirrhosis and hepatocellular carcinoma. Animal models—from rodents to guinea pigs, minipigs and genetically hypertensive rats—are indispensable for dissecting the molecular networks of lipid accumulation, oxidative stress and immune activation. By recapitulating human-relevant pathological features, these models yield insight into metabolic flux, gene expression and the efficacy of novel interventions, thereby guiding translational strategies for diagnosis and treatment of hepatic metabolic disorders.

Research from Nature Portfolio

A long-term study in Bama minipigs fed a high-fat, high-sucrose diet for 23 months revealed early-stage NASH characterised by hyperinsulinaemia, de novo lipogenesis and ketone body production. Elevated hepatic iron and overexpression of cytochrome P450 2E1 promoted reactive oxygen species and lipid peroxidation, mirroring key aspects of human disease. Transcriptome profiling identified dysregulated pathways in fatty acid synthesis and antioxidant defence, establishing this large-animal model as a robust platform for investigating metabolic drivers of steatohepatitis.

Metabolic Disorders and Animal Models in Hepatic Health publication trend

The graph below shows the total number of articles in metabolic disorders and animal models in hepatic health across all publications each year (not limited to Nature Index journals).

Technical terms

Non-alcoholic fatty liver disease (NAFLD): Accumulation of excess fat in the liver not due to alcohol consumption.

Non-alcoholic steatohepatitis (NASH): Inflammatory progression of NAFLD characterised by liver cell damage and inflammation.

Steatosis: Excessive lipid deposition within hepatocytes.

Fibrosis: Excessive deposition of extracellular matrix proteins leading to scar tissue formation.

Hepatocyte ballooning: Swelling of liver cells indicating cellular injury.

Hyperinsulinaemia: Abnormally high insulin levels in the bloodstream.

Reactive oxygen species (ROS): Chemically reactive oxygen‐derived molecules that can cause oxidative stress.

Ketone bodies: Metabolic fuels produced from fatty acid oxidation during energy deficit.

References

1. Dietary Long-Chain Fatty Acids Accelerate Metabolic Dysfunction in Guinea Pigs with Non-Alcoholic Steatohepatitis. Nutrients (2023).
2. Differentially Expressed Genes in Response to a Squalene-Supplemented Diet Are Accurate Discriminants of Porcine Non-Alcoholic Steatohepatitis. International Journal of Molecular Sciences (2023).
3. Development of novel rat model for high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr. Environmental Health and Preventive Medicine (2011).
4. Hyperinsulinemia shifted energy supply from glucose to ketone bodies in early nonalcoholic steatohepatitis from high-fat high-sucrose diet induced Bama minipigs. Scientific Reports (2015).