The impacts of a novel translatable Western diet on multi-organ physiology

Diet plays a major role in health and disease and diet-based disease models are common in research. However, the majority of diet-induced disease models in rodents lack translatability. These models often use megadoses of nutrients, such as fat, or feature deficiencies uncommon in humans to induce disease. As such, there is major need to explore more translatable diet models to better understand disease physiology. The objectives of this study were to determine the multi-organ effects of a novel Western diet in male and female mice. We hypothesize our novel translatable Western diet will result in multi-organ disease that more similarly mimics what is seen in humans. Male and female C57BL/6 mice (n=6-10/sex/group) were randomly divided between a control diet (AIN-93G) and our novel Western diet and allowed to eat ad libitum for 12 weeks. The novel Western diet is high in fat and sugar, with specific focus on mimicking the American diet, including high saturated fat, a high n-6:n-3 fatty acid ratio, high sucrose and fructose, and low dietary fiber. Food consumption, weight, and water consumption were measured regularly. Mice consuming the novel translatable Western diet displayed histological evidence of steatotic liver disease, abnormalities in heart physiology, decreased sexual organ weight, and alterations in standard serum measures of health, such as transaminases, glucose, and potassium. More in-depth analyses are currently being conducted to further define the model. In conclusion, a novel translatable Western diet model in mice induces several features of diet-driven disease across many organ systems and more research will untangle the mechanisms by which the diet induces disease. Funding provided by the UVM Food Systems Research Center via a Non-Assistance Cooperative Agreement with the USDA Agricultural Research Service This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.