Mechanisms by which macronutrients program postnatal 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可能对成年后的后代有害。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。人们对母亲营养过剩及其对后代的持久影响知之甚少。更复杂的是，新出现的证据表明，早期营养与成年期营养之间的不匹配程度越大，代谢紊乱的风险就越大。因此，我们的目标是确定将后代与其母亲在怀孕期间的饮食重新匹配是否可以减少他们在食用高脂肪/高糖饮食后所经历的一些有害影响。我们假设或预测，将后代与高膳食纤维的母体饮食重新匹配将产生保护作用，而与高蛋白质的母体饮食重新匹配将对后代成年后产生有害影响。我们将在这项资助中解决的具体目标是：1)检查在8周高脂肪/蔗糖饮食挑战后，重新匹配后代与母亲的饮食是否会对后代的代谢健康产生有益的影响；2)确定与母体高益生元纤维或蛋白质饮食重新匹配的后代肠道结构是否会发生变化；3)确定高蛋白质或益生元纤维的母体饮食是否会改变母乳成分；4)确定高益生元纤维的产后饮食是否可以逆转与产前环境受损相关的发育程序。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。研究高纤维和高蛋白质饮食的影响，在发育文献中是一个相对未被触及的领域，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 when 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 about maternal over-nutrition and the lasting effects it has on offspring. To add to the complexity emerging evidence suggests that the greater the degree of mismatch between early nutrition and that encountered in adulthood the greater the risk of metabolic disturbance. Our goal, therefore, is to determine if re-matching offspring to the diet their mother consumed during pregnancy can reduce some of the detrimental effects they experience after consuming a high fat/sugar diet. We hypothesize or predict that re-matching offspring to a maternal diet high in dietary fiber will program protective effects and re-matching to a maternal diet high in protein will program detrimental effects in offspring as adults. The specific objectives we will address in this grant are: 1) to examine whether re-matching offspring to maternal diet will have beneficial effects on metabolic health of offspring after an 8 wk high fat/sucrose diet challenge; 2) to determine whether changes in the structure of the intestine occurs in offspring re-matched to maternal diets high in prebiotic fiber or protein; 3) to determine if maternal diets high in protein or prebiotic fiber alter maternal milk composition; 4) to determine whether a postnatal diet high in prebiotic fiber can reverse the developmental programming associated with a compromised prenatal environment. The overall goal of this proposal is to undertake basic research on how dietary patterns during fetal development affect glucose and lipid metabolism. Results of this work will provide important insight into the factors involved in the developmental origins of health and disease. Examining the impact of high fiber and protein diets, a relatively untouched area in the developmental literature, is likely to greatly expand our knowledge of how nutrition programs the health of the fetus for life.