Diet-Induced Metabolic Dysfunction in Rodent Models

Rodent models of diet-induced metabolic dysfunction have become indispensable tools for unraveling the pathophysiology of obesity, insulin resistance and associated comorbidities. Feeding rodents a high-fat or cafeteria diet recapitulates key features of human metabolic syndrome, including visceral adiposity, chronic low-grade inflammation and dyslipidaemia. These interventions elicit hepatic steatosis through impaired mitochondrial fatty acid oxidation and provoke a proinflammatory milieu in adipose tissue driven by altered adipokine secretion. Variations in diet composition, duration and rodent strain allow dissection of genetic and environmental contributions to metabolic imbalance. Such models yield insights into the interplay between nutrient overload, organ-to-organ crosstalk and systemic oxidative stress, offering a translational platform to evaluate novel therapeutic strategies and nutritional interventions aimed at curbing the global burden of obesity-related diseases.

Research from Nature Portfolio

Recent studies have compared distinct obesogenic diets in mice to refine model selection for cardiometabolic investigations. One investigation assessed a standard chow, normal-fat, cafeteria and high-fat diet over 12 weeks in C57BL/6J mice, demonstrating that both cafeteria and high-fat regimens induce comparable weight gain and glucose intolerance, but that cafeteria feeding more severely impairs perivascular adipose vasodilatory function. Reduced phosphorylation of endothelial nitric oxide synthase and enhanced coagulation activity emerged as diet-specific vascular end points. In another study, maternal supplementation with grape seed procyanidins during lactation was shown to programme offspring metabolism: despite elevated adiponectin levels, progeny exhibited hyperinsulinaemia, reduced adiponectin receptor expression and muscle AMPK signalling, pointing to an adiponectin-resistance phenotype induced by altered milk lipid content.

Diet-Induced Metabolic Dysfunction in Rodent Models publication trend

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

Technical terms

High-fat diet: A rodent feeding protocol in which 40–60% of caloric intake is derived from lipids, used to induce obesity and related metabolic changes.

Cafeteria diet: A diet model comprising varied, palatable human snack foods to mimic Western eating patterns and promote voluntary hyperphagia.

Insulin resistance: A state of diminished cellular responsiveness to insulin, resulting in impaired glucose uptake and elevated circulating glucose.

Adipokines: Bioactive proteins secreted by adipose tissue that regulate appetite, inflammation and metabolic homeostasis.

Mitochondrial dysfunction: A decline in mitochondrial oxidative capacity that impairs fatty acid oxidation and increases oxidative stress in tissues.

References

1. Crosstalk between Adipose Tissue and Hepatic Mitochondria in the Development of the Inflammation and Liver Injury during Ageing in High-Fat Diet Fed Rats. International Journal of Molecular Sciences (2023).
2. Effects of different diets used in diet-induced obesity models on insulin resistance and vascular dysfunction in C57BL/6 mice. Scientific Reports (2019).
3. Maternal intake of grape seed procyanidins during lactation induces insulin resistance and an adiponectin resistance-like phenotype in rat offspring. Scientific Reports (2017).
4. TetraSOD®, a Unique Marine Microalgae Ingredient, Promotes an Antioxidant and Anti-Inflammatory Status in a Metabolic Syndrome-Induced Model in Rats. Nutrients (2022).
5. Cafeteria diet increased adiposity in comparison to high fat diet in young male rats. PeerJ (2019).