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Research article
Comparative analysis of the impact of a high-fat, high-carbohydrate diet on two generations of naïve mice
Ayman Alhazmi, Mamdouh Allahyani
Abstract: Background: A maternal high-fat diet influences offspring and may elevate their susceptibility to obesity and type 2 diabetes mellitus. This study aims to examine the impact of a high-fat, high-carbohydrate diet on the development of obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, and cardiovascular disease in mice and their progeny. Methods: Twenty one-month-old BALB/c mice (10 males and 10 females) were divided into control and first-generation groups of five males and five females. The control mice ate a butter-based diet with 10%–11% fat calories, while the first-generation mice ate 45% fat and 30% carbohydrates. The weights of both groups were measured for 4 months. In the first generation, females and males cohabited and mated. Mothers ate a high-fat, high-carbohydrate diet throughout pregnancy and nursing. After weaning, 10 second-generation pups (five males and five females) were randomly picked and isolated from their mothers in other cages. Isolated weaned offspring ate a high-fat, high-carbohydrate diet for 4 months. Several biochemical parameters were estimated for each mouse in the three groups. Results: Higher levels of random blood glucose, triglycerides, total cholesterol, and LDL-C were seen in the second generation than in the first generation, whereas lower HDL-C was observed in the second generation. The second generation had considerably greater HbA1c levels than the first generation. Significantly greater liver enzyme activity was seen in the second generation. Proteinuria was observed in the second generation. Second-generation mice had greater total CK and CK-MB activity. The second-generation group showed considerably lower nitric oxide and adropin levels than the first-generation group. The second-generation mice had greater serum endothelin-1 and vascular endothelial growth factor levels than the first-generation mice. Conclusions: The study concludes that a high-fat, high-carbohydrate diet induces obesity and T2DM in mice. The offspring of mothers that consume a high-fat, high-carbohydrate diet during both prenatal and postnatal periods exhibit a greater risk of developing these diseases than their progenitors.
Keywords: high-fat high-carbohydrate diet, obesity, non-alcoholic fatty liver disease, type 2 diabetes mellitus
Received: 7.7.2025
Accepted: 2.12.2025
Published: 23.1.2026
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