Dietary, energy balance, and behavioural factors affecting postprandial fructose metabolism and the impact on normal glucose and lipid metabolism.

自20世纪70年代以来，加拿大人的果糖摄入量显著增加，并在过去十年中一直保持在较高水平。膳食果糖来源主要包括加工或工业加工食品，果糖(例如甘蔗和甜菜糖或高果糖玉米糖浆)是一种对北美农业和食品工业特别重要的全球主要商品(即高果糖玉米糖浆)。然而，大多数已知的关于哺乳动物果糖代谢的研究报告没有使用与生理相关的长期摄入量或短期极高的摄入量。需要更好地了解果糖代谢的基本生物学和生理学知识，特别是在餐后阶段。这项研究计划将使用两种动物模型和稳定同位素技术，以更好地了解餐后果糖代谢与正常糖脂代谢之间的关系。首先，使用高果糖喂养的C57BL/6J小鼠模型，本项目将检验长期暴露和增加果糖摄入量会扰乱餐后血糖和脂肪代谢的假说，并产生肝脏含量增加、胰岛素抵抗和异常脂质运输的表型。将在老鼠身上进行进一步的研究，以确定性别、能量平衡和运动训练在果糖餐后代谢中所起的作用。其次，使用多导管猪模型(即尤卡坦小型猪，与人类胃肠道高度同源的成熟模型)，本计划将研究在餐后特定器官(即小肠、肝脏和周围组织)内和特定器官之间果糖是如何代谢的。小肠和肝脏在果糖、葡萄糖和脂肪的代谢中起着关键作用。因此，了解这些组织如何在餐后增加摄入量的情况下代谢果糖，对于了解果糖如何影响正常的葡萄糖和脂肪代谢至关重要。这套实验(超过5年的NSERC DG周期)将通过饮食(例如高热量和低热量梯度)和运动训练(例如机动跑步机)在高果糖喂养和不喂食高果糖的情况下谨慎地操纵能量平衡。将收集和分析生理(例如间接量热法、体重增加、身体组成)、生化(例如血糖、血脂、胰岛素)和功能(例如稳定同位素的脂肪生成)的数据，以确定果糖对肝脏脂肪代谢失调和相关表型的相对贡献。

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.