Influence of nutrients on developmental programming of metabolism

有令人信服的证据表明，生命早期的营养影响可以永久地影响成年后的健康。一系列动物研究表明，母亲在怀孕期间营养不良会对成年后的后代造成伤害。与营养良好的雌性大鼠相比，营养不良的后代往往更容易出现体重、血糖控制和脂质（脂肪）代谢紊乱。然而，关于母亲营养过剩及其对后代的持久影响，我们所知甚少。某些饮食成分的过度营养可能是保护或有害的。我们希望研究的两种饮食疗法是高纤维和高蛋白。因此，我们的目标是确定母体饮食对后代脂质和葡萄糖代谢发育程序的影响。我们假设或预测，高膳食纤维的母体饮食会对后代产生保护作用，而高蛋白质的母体饮食会对后代产生有害影响。在这项资助中，我们将解决的具体目标是：1)确定高纤维或高蛋白质的母亲饮食对后代成年后脂质和葡萄糖代谢的长期影响。2)确定高膳食纤维或高蛋白质的母亲饮食对母亲和子代肠道细菌谱的影响。肠道中的某些细菌可以增加从食物中获取的能量，增加身体脂肪。3)确定产前和产后营养环境不平衡的影响。不匹配的环境可能更有害。4)确定高膳食纤维的产后饮食是否可以逆转与产前营养受损相关的负面发育程序。本提案的总体目标是开展胎儿发育期间饮食模式如何影响糖脂代谢的基础研究。这项工作的结果将为健康和疾病的发育起源所涉及的因素提供重要的见解。高摄入膳食纤维和蛋白质的影响，在发育文献中是一个相对未触及的研究领域，可能会极大地扩展我们对营养计划如何影响胎儿终身健康的认识。

There is convincing evidence that nutritional influences early in life can permanently program adult health. A range of animal studies have shown that maternal under-nutrition during pregnancy can be harmful to the offspring once they reach adulthood. Disturbances in body weight, blood glucose control and lipid (fat) metabolism often present to a greater extent in offspring of undernourished versus well-nourished female rats. Much less is known, however, about maternal over-nutrition and the lasting effects it has on offspring. Over-nutrition of certain dietary components has the potential to be either protective or detrimental. The two dietary treatments we wish to examine in this grant are high fiber and high protein. Our goal, therefore, is to determine the effect of maternal diet on developmental programming of lipid and glucose metabolism in offspring. We hypothesize or predict that maternal diets high in dietary fiber will program protective effects and those high in protein will program detrimental effects in offspring. The specific objectives we will address in this grant are: 1) Determine the long-term effects of a maternal diet high in fiber or protein on lipid and glucose metabolism in offspring once they reach adulthood. 2) Determine the effect of maternal diet high in dietary fiber or protein on gut bacterial profiles of mothers and offspring. Certain bacteria in the gut can increase energy harvest from food and increase body fat. 3) Determine the effect of an imbalance between prenatal and postnatal nutritional environment. Mismatched environments may be more harmful. 4) Determine whether a postnatal diet high in dietary fiber can reverse the negative developmental programming associated with compromised prenatal nutrition. The overall goal of this proposal is to undertake basic research on how dietary patterns during fetal development affect glucose and lipid metabolism. The results of this work will provide important insight into the factors involved in the developmental origins of health and disease. The impact of high intakes of dietary fiber and protein, a relatively untouched area of research in the developmental literature, is likely to greatly expand our knowledge of how nutrition programs the health of the fetus for life.