CEPHALIC RESPONSES AND MEAL FEEDING

描述（由申请人提供）：许多系统参与导致动物寻找和摄取食物的综合过程，并在有更多食物时停止进食。这个项目与一次性摄入大量卡路里的急性效应有关，因为尽管为身体提供新的营养是饮食的最终目标，但它只能通过扰乱循环营养的微妙平衡来实现，至少是暂时的。正因为如此，动物已经进化出了精心设计的策略，以尽量减少膳食对血糖和其他营养素的急性影响。这些适应性反应中有许多是在预期要吃大餐时做出的，它们及其后果是本提案的重点。我们还发现，在短时间内消耗所有日常食物的膳食喂养动物在期待食物时大大提高了葡萄糖耐量。 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。 根据我们的新观察，我们制定了三个具体目标。具体目标1将利用正常血糖高胰岛素或高血糖钳夹来鉴定负责改善葡萄糖耐量的代谢适应，测试关于外周胰岛素抵抗、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。具体目标2将检验一个假设，即当自由进食的大鼠预期吃大餐时，会发生一系列类似的食物预期反应。具体目标3将检验这样的假设，即膳食喂养的大鼠能够在短时间内吃大量的食物，因为它们对饱腹感信号变得相对无反应。这个项目将确定改善葡萄糖耐量的行为方法。由于葡萄糖耐量受损是糖尿病和许多肥胖症的主要症状，并且由于大多数当前疗法仅实现葡萄糖耐量的适度改善，因此所提出的研究具有相当大且令人信服的健康意义;即，根据这项研究，针对葡萄糖耐量受损患者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.