Grant: Discovery Grants Program - Individual

Dietary fructose intakes of Canadians have significantly increased since the 1970s and have remained consistently high for the last decade. Dietary fructose sources mainly include processed or industrially prepared foods and fructose (e.g. cane and beet sugar or high fructose corn syrup) is a major worldwide commodity particularly important to the North American agricultural and food industries (i.e. high fructose corn syrup). However, most of what is known about the metabolism of fructose in mammals are reported in studies not using physiologically relevant long-term intakes or short-term extremely high amounts. A better basic biological and physiological understanding of fructose metabolism, particularly in the postprandial period is needed. This program of study will use two animal models and stable isotope techniques to better understand the relationship between postprandial fructose metabolism and normal glucose and lipid metabolism. Firstly, using high fructose feeding C57BL/6J mouse model this program will test the hypothesis that long-term exposure and increasing fructose intake dysregulates postprandial glucose and lipid metabolism and produces a phenotype of increased hepatic liver content, insulin resistance and aberrant lipid trafficking. Additional studies in mice will be conducted to determine the role sex, energy balance and exercise training play in the postprandial metabolism of fructose. Secondly, using a multiple catheterization pig model (i.e. Yucatan miniature pig, well-established model with high degree of gastrointestinal tract homology with humans) this program will study how fructose is metabolized in and between specific organs (i.e. small intestine, liver, and peripheral tissues) during the postprandial period. The small intestine and liver play pivotal roles in the metabolism of fructose, as well as glucose and lipids. Therefore, characterizing how these tissues metabolize fructose with increasing intake in the postprandial period is critical to understanding how fructose impact normal glucose and lipid metabolism. This set of experiments (over 5 year NSERC DG cycle) will carefully manipulate energy balance through diet (e.g. hyper and hypocaloric gradient), and exercise training (e.g. motorized treadmill) with and without high fructose feeding. Physiological (e.g. indirect calorimetry, weight gain, body composition), biochemical (e.g. blood glucose, lipids, insulin) and functional (e.g. lipogenesis by stable isotope) data will be collected and analyzed to determine the relative contribution of fructose to dysregulation of hepatic lipid metabolism and the related phenotype.