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规划成人健康。一系列动物研究表明，母亲在怀孕期间营养不良可能对后代成年后有害。与营养良好的雌性大鼠相比，营养不良的雌性大鼠的后代在体重、血糖控制和脂质（脂肪）代谢方面往往存在更大程度的紊乱。关于母亲营养过剩及其对后代的持久影响，人们所知甚少。为了增加复杂性，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重新匹配到他们母亲在怀孕期间食用的饮食是否可以减少他们在食用高脂肪/糖饮食后所经历的一些不利影响。我们假设或预测，将后代重新匹配到富含膳食纤维的母体饮食将产生保护作用，而重新匹配到富含蛋白质的母体饮食将对后代成年后产生有害影响。本研究的具体目标是：1）研究在8周高脂肪/蔗糖饮食挑战后，将后代与母体饮食重新匹配是否会对后代的代谢健康产生有益影响; 2）确定在与富含益生元纤维或蛋白质的母体饮食重新匹配的后代中是否会发生肠道结构的变化; 3）确定高蛋白质或益生元纤维的母体饮食是否改变母乳成分; 4）确定高益生元纤维的产后饮食是否可以逆转与受损的产前环境相关的发育编程。这项提案的总体目标是进行关于胎儿发育期间饮食模式如何影响葡萄糖和脂质代谢的基础研究。这项工作的结果将提供重要的洞察健康和疾病的发展起源所涉及的因素。研究高纤维和蛋白质饮食的影响，在发育文献中相对未触及的领域，可能会大大扩展我们对营养如何规划胎儿健康的知识。

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.