A Western-type diet, not fructose content, differentially impacts cardiometabolic outcomes in male versus female mice

In the last 30 years, worldwide dietary sugar consumption has increased drastically and daily energy from sugar in North America is approximately 20% (Marriott, 2009). Fructose comprises approximately half of these intakes – primarily as sucrose and high-fructose corn syrup (HFCS). High fructose intakes have been linked to dysregulation in hepatic carbohydrate and lipid metabolism, leading to an increased cardiometabolic risk. The objective of this study was to identify fructose and sex-specific changes on different cardiometabolic risk factors in mice; we hypothesized that these phenotypic changes would only present when fructose intake was matched with hypercaloric intakes. To test this hypothesis, adult male and female C57BL/6J mice (18-weeks old) consumed a high-fat, high-sugar, hypercaloric diet consisting of either 0% (n=17), 10% (n=17), or 20% (n=18) of total calories from fructose for 18-weeks. A bolus dose of glucose and stable isotope U-13C-fructose (0.5 g/kg body weight (BW) respectively) was administered by gavage 30-minutes before the animals were killed. The following sex-specific differences were observed: males displayed greater BW gain per week (1.19 g/week, p<0.001) and liver weight per gram BW (8.33%, p<0.001) than their female counterparts (0.76 g/week, 6.47%), and females displayed higher blood glucose concentrations (20.4 mmol/L, p<0.05) at the 30-minute timepoint in comparison to males (17.8 mmol/L). Amongst treatment groups, no differences were observed for BW gain per week, liver weight per gram BW, or blood glucose concentrations (baseline, 15-min, 30-min post-gavage). In addition, the coronary arteries and the aorta were free of atherosclerotic lesions and appeared normal with intact endothelia lining for all treatment groups. This preliminary data suggests that a diet high in fat and energy, rather than fructose, may differentially impact cardiometabolic outcomes when assessed in males versus females. Current analysis of liver and cardiac lipid profiles (measured by GC) as well as stable isotope U-13C-fructose tracer/tracee ratios (measured by GC-MS) will help to further investigate if fructose intake differentially impacts the carbohydrate or lipid metabolism at the whole-body level and within specific tissues. Continuing this research is critical to providing insight on the dysregulation of carbohydrate and lipid metabolism associated with fructose consumption. (Funded by NSERC)