Effects of diet on metabolic programming of glucose homeostasis

我的NSERC资助的研究项目的长期目标是了解在生长和发育的敏感时期摄入营养对人体在一生中不同时期控制血糖的过程的影响。我的工作以一种名为“健康与疾病的发育起源”(DOHAD)的实验范式为基础，专注于在一生的生长和发育敏感期摄入果糖(FR)对代谢的影响；控制脂肪组织沉积在我的工作中很重要。工作假设是，在这些时期暴露于FR会对协调血糖控制的代谢系统产生负面影响。我研究膳食FR是因为众所周知它会导致胰岛素抵抗和高循环胰岛素水平，而且它与当今社会相关。加拿大人每天总卡路里的21%来自糖，其中约50-60克是FR。超过35%的糖消耗来自添加的糖(即在准备、加工或在餐桌上添加)。我选择研究FR对怀孕的影响，因为怀孕和哺乳期是已知的生长发育最敏感的时期，怀孕期间糖的摄入量会增加。 这项赠款周期中的研究将1)研究怀孕和哺乳期间的饮食摄入是否会导致母亲身体发生变化，从而导致随后怀孕时体脂增加和血糖控制不佳；2)确定怀孕期间高FR摄入量(男性)或怀孕(女性)与母亲怀孕期间高FR摄入量之间的相互作用，以及母亲在怀孕期间摄入高FR对代谢的持久影响。我特别感兴趣的是身体肥胖和控制血糖。 我的研究结果是理解饮食FR具有负面和持久影响、促进体脂增加和血糖控制不良的机制的基础。这对于理解基础生物学具有重要意义，并将帮助我们确定新的方法，以预防一生中和未来几代人的血糖控制和过度肥胖问题。

The long-term objective of my NSERC-funded research program is to understand the impact of nutritional intake during sensitive periods of growth and development on processes in the body controlling blood glucose at different times across the lifespan. My work is grounded in an experimental paradigm called the "Developmental Origins of Health and Disease" (DOHAD) and focuses on the metabolic effects of dietary fructose (FR) intake during sensitive periods of growth and development across the lifespan; control of adipose tissue deposition is important in my work. The working hypothesis is that exposure to FR during these periods negatively affects the metabolic systems that coordinate the control of blood glucose. I study dietary FR because it is known to induce insulin resistance and high circulating levels of insulin, and because it is relevant in today's society. Canadians consume ~21% of their total daily calories from sugars, of which ~50-60 g is FR. More than 35% of sugar consumed is from added sugars (i.e. added during preparation, processing or at the table). I chose to study the effects of FR in pregnancy because gestation and lactation are the most sensitive periods of growth development known, and sugar intake increases during pregnancy. Studies in this grant cycle will 1) examine whether dietary intake in pregnancy and lactation causes changes in the mother's body that contribute to increased body fatness and poor control of blood glucose in a subsequent pregnancy, and 2) define the interactions between high FR intake (in males), or pregnancy (in females), and the lasting metabolic effects of having had a mother with high FR intake during preganncy. My specific interests are in terms of body fatness and control of blood glucose. Results from my studies are fundamental to understanding mechanisms by which dietary FR has negative and lasting effects and promotes increased body fatness and poor blood glucose control. It is significant for understanding basic biology and will help us to identify new approaches to preventing problems in glucose control and excessive adiposity across the lifespan and in future generations.