Effect of Combined In-Utero and Lifelong Exposure to Dietary Sugars on Offspring Metabolic Health in Mice

OBJECTIVES: Carbohydrates are the most abundant macronutrient in the diet, their quality is paramount to good metabolic health. The glycaemic index (GI) measures carbohydrate quality based on postprandial blood glucose levels, with lower GI foods associated with better metabolic health. This study compared sugars with a range of GIs from glucose (highest), sucrose (middle) and isomaltulose (lowest). METHODS: C57BL/6J female mice were fed one of three isocaloric sugar diets or an AIN93-G control and mated with chow males. Pups continued their mother's diet until 30-weeks. Body composition was determined by EchoMRI, feeding behaviour by BioDAQ and oral glucose tolerance tests (OGTT) performed. RESULTS: Female pups fed sugar diets were fatter by 30-weeks compared to controls. In male mice, glucose-fed pups were heavier, and all sugar-fed pups were fatter compared to controls. Female sugar pups secreted more insulin in response to glucose and insulin peak was delayed in mice fed isomaltulose. At both 12- and 24-weeks, sugar fed mice ate for shorter periods of time (AIN93-G vs glucose p < 0.01; vs sucrose p < 0.05; vs isomatulose p < 0.001) compared to AIN93-G mice but ate more frequently (AIN93-G vs glucose p < 0.05; vs sucrose p < 0.001; vs isomatulose p < 0.001) and had increased food intake over 24 hours (AIN93-G vs sucrose p < 0.05; vs isomatulose p < 0.05). Interestingly, at 24-weeks food intake was reduced, compared to 12-weeks in sugar-fed mice. These results may be due to the increased presence of liver fibrosis observed in 32% of glucose-, 38% of sucrose- and 24% of isomaltulose-fed mice and corroborated with histology. At 30-weeks AIN93-G mice had larger caecum's than their sugar-fed counterparts frequently (AIN93-G vs glucose p < 0.05; vs sucrose p < 0.01; vs isomatulose p < 0.05). CONCLUSIONS: These results suggest female mice are more heavily affected at 30-weeks across all sugar diets with a higher body weight, percent fat, insulin response to an OGTT, increased food intake, liver fibrosis and caecum weight. Male mice show less differences in weight but sugar still negatively effects body composition, food intake, liver fibrosis and caecum weight. These findings show that free sugars, regardless of their GI can induce changes in body composition and risk of metabolic disease. FUNDING SOURCES: The University of Sydney.