Animal Models of Diet-Induced Obesity and Metabolic Disorders

Animal models of diet-induced obesity (DIO) and metabolic disorders have become indispensable for unravelling the multifaceted mechanisms that underlie obesity, insulin resistance and related comorbidities. Rodent models, most commonly mice and rats, are fed specialised diets—often high in fat, sugar or both—to mimic the nutritional imbalances seen in human populations. These protocols generate progressive weight gain, adipose tissue expansion, low-grade inflammation, dyslipidaemia and impaired glucose homeostasis. The choice of strain, sex and diet composition determines the phenotypic spectrum, from early insulin insensitivity to overt type 2 diabetes and hepatic steatosis. Genetic backgrounds such as C57BL/6 and outbred lines differ in susceptibility, enabling investigation of gene–environment interactions. In addition to standardised high-fat regimens, novel combinations of carbohydrates and saturated fats have refined the onset and severity of metabolic disturbances. Beyond rodents, zebrafish and Drosophila models offer high-throughput platforms for screening dietary components and genetic modifiers. Collectively, these models have elucidated adipocyte biology, systemic inflammatory pathways and central appetite networks, while also serving as test beds for emerging pharmacological and nutritional interventions. The resulting insights continue to inform translational strategies aimed at more effective prevention and treatment of obesity-linked disorders worldwide.

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Animal Models of Diet-Induced Obesity and Metabolic Disorders publication trend

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

Technical terms

Diet-induced obesity (DIO): Experimental weight gain in animals resulting from defined dietary regimens high in fats, sugars or both.

High-fat diet (HFD): A formulation containing an elevated proportion of calories from fat, used to induce obesity and insulin resistance in models.

White adipose tissue (WAT): The primary site of energy storage in the form of triglycerides and a source of inflammatory mediators in obesity.

Insulin resistance: A diminished cellular response to insulin leading to impaired glucose uptake and compensatory hyperinsulinaemia.

Hepatic steatosis: Excess accumulation of lipids in liver cells, often accompanying obesity and predisposing to non-alcoholic fatty liver disease.

References

1. Trapped fat: Obesity pathogenesis as an intrinsic disorder in metabolic fuel partitioning. Obesity Reviews (2024).
2. Mesenchymal-specific Alms1 knockout in mice recapitulates metabolic features of Alström syndrome. Molecular Metabolism (2024).
3. Diet-induced obesity in animal models: points to consider and influence on metabolic markers. Diabetology & Metabolic Syndrome (2021).