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Determining the impact of fructose and glucose and their interactions with dietary fat on metabolic health

Harrison Facey

Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia

Nutrition is arguably the most dominant factor that impacts health and longevity. Research utilising the ‘Geometric Framework’ (GF), a state-space nutritional modelling method, has elucidated that low protein-high carbohydrate diets in mice result in the longest lifespan, and that high-protein diets are the major detriment for metabolic health. However, hyperpalatable foods that are associated with obesity and diabetes are rich in sugars and fat. Our aims in this study were to compare the effects of consuming glucose and fructose – the two major dietary monosaccharides - on metabolic health, and to examine the nature of their interaction with dietary fat, and its impact on obesity and insulin resistance. Male C57BL6 (n=244) mice were fed ad-libitum one of 15 isocaloric diets (n=12-16/diet) with low (10:70), medium (20:60), or high (30:50) fat:carbohydrate energy for 18 weeks, with protein fixed at 20%. The composition of carbohydrate was 30% fixed as starch (complex carbohydrate) in all diets, with the remaining 70% made up of monosaccharide forms of fructose or glucose or their combinations (100:0, 75:25, 50:50, 25:75, 0:100). Food intake and body weights were measured weekly, in vivo metabolic health was assessed by glucose tolerance tests after 5-6 and 13-15 weeks of dietary intervention, metabolic cage testing and insulin tolerance tests, and tissues were harvested after 17-18 weeks. GF analysis of the data revealed that combined intake of fructose and glucose led to the worst metabolic health (increased energy intake and body weight, highest fat mass and worst insulin sensitivity). Glucose tolerance was worst on high fat intake coupled with co-ingestion of glucose and fructose. Peak liver triglyceride content was seen on combined glucose and fructose ingestion on a relatively lower fat background. Overall, co-ingestion of fructose and glucose was found to be worst for metabolic health than their consumption in isolation.