CEPHALIC RESPONSES AND MEAL FEEDING

描述（由申请人提供）：许多系统参与了导致动物寻找和摄入食物的综合过程，并在有更多食物时停止进食。这个项目与一次摄入大量卡路里的急性效应有关，因为虽然为身体提供新的营养物质是饮食的最终目标，但它只能通过扰乱循环营养物质的微妙平衡来实现，至少是暂时的。正因为如此，动物们进化出了复杂的策略，以尽量减少食物对血糖和其他营养物质的严重影响。这些适应性反应中的许多都是在预期吃大餐时产生的，它们和它们的后果是本提案的重点。我们还发现，在短时间内消耗掉所有日常食物的膳食喂养动物，在它们期待食物的时候，它们的葡萄糖耐量会大大提高。该项目的目标是了解这种适应的机制，以便为未来的治疗提供信息。基于我们的新观察，我们制定了3个具体目标。特异性目标1将利用正糖型高胰岛素或高血糖钳来确定改善葡萄糖耐量的代谢适应，测试有关外周胰岛素抵抗、葡萄糖处置率和/或b细胞功能变化的特定假设。这些实验将使用实验室大鼠和小鼠。特异性目标2将测试一个假设，即当自由喂养的大鼠预期吃大餐时，会发生类似的食物预期反应。Specific Aim 3将测试这样一个假设，即膳食喂养的大鼠能够在短时间内吃下大量食物，因为它们对饱腹感信号的反应相对迟钝。该项目将确定改善葡萄糖耐量的行为方法。由于糖耐量受损是糖尿病和许多肥胖病例的主要症状，并且由于目前大多数治疗方法仅能适度改善糖耐量，因此提出的研究具有相当大的和引人注目的健康意义；也就是说，根据拟议的研究，针对糖耐量受损个体的新疗法可能包括特定的饮食方案，这些方案将产生强大的健康益处，以补充药理学方法。

DESCRIPTION (provided by applicant): Numerous systems participate in the integrated processes that cause an animal to seek and ingest food, and to stop eating when more food is available. This project relates to the acute effects of ingesting large numbers of calories at 1 time, for whereas supplying new nutrients to the body is the ultimate goal of eating, it can only be accomplished by perturbing the delicate balance of circulating nutrients, at least on a temporary basis. Because of this, animals have evolved elaborate strategies to minimize the acute impact of meals on blood glucose and other nutrients. Many of these adaptive responses are made in anticipation of eating large meals, and they and their consequences are the focus of this proposal. We have also found that meal-fed animals that consume all of their daily food in a short period of time have greatly improved glucose tolerance at the time they are expecting food. The goal of this project is to understand the mechanisms underlying this adaptation in order to inform future therapies. Based upon our novel observations, we have developed 3 specific aims. Specific Aim 1 will utilize euglycemic hyperinsulinemic or hyperglycemic clamps to identify the metabolic adaptations responsible for improved glucose tolerance, testing specific hypotheses concerning changes in peripheral insulin resistance, glucose disposal rate and/or B-cell function. These experiments will utilize laboratory rats and mice. Specific Aim 2 will test the hypothesis that a comparable battery of food anticipatory responses occurs when ad lib-fed rats anticipate eating large meals. Specific Aim 3 will test the hypothesis that meal-fed rats are enabled to eat large amounts of food in a short period of time because they have become relatively unresponsive to satiety signals. This project will identify behavioral approaches that improve glucose tolerance. Because impaired glucose tolerance is a major symptom of diabetes mellitus and many instances of obesity, and because most current therapies achieve only modest improvements in glucose tolerance, the proposed research has considerable and compelling health implications; i.e., based on the proposed research, novel therapies for individuals with impaired glucose tolerance might include specific eating regimens that would yield powerful health benefits to complement pharmacological approaches.