HYPOTHALAMIC NEUROTRANSMITTER SYSTEMS & EATING BEHAVIOR

描述(摘自申请者的摘要)：肥胖普遍存在， 在工业化社会中不断增长。已知的一个重要因素是 高脂肪或高卡路里饮食的出现也促进了这一增长。另一个 需要考虑的因素是个体由于遗传因素导致体重增加的倾向。 或早期环境影响。这项研究的目标是使用 研究脑肽在饮食中的作用的创新方法 以及性情。这些神经化学物质是甘丙素(GAL)和神经肽Y (NPY)，已知在下丘脑刺激进食行为和 减少能量消耗，但谁在肥胖中的具体作用仍然存在 将被澄清。这项研究的一个主要目标是确定在 模拟人类情况的饮食肥胖模型，这些多肽具有 饮食障碍和体重控制的因果关系。 具体地说，它假设：a)GAL，在大脑的特定神经元中 室旁核(PVN)投射到正中隆起(ME)， 会导致体重增加和肥胖症 高脂饮食；以及b)投射在弓状核(ARC)神经元中的NPY 对于PVN，过量的高卡路里饮食会导致体重增加 碳水化合物。这项研究计划已扩大到包括新的 实验模型和技术；行为的同时分析， 内分泌、代谢和神经化学参数；以及不同 动物种群。拟议的实验将在以下方面进行调查：1)具体 目的1、过量进食引起的神经生物学和代谢系统的改变 高脂肪或高碳水化合物饮食的大鼠；2)特定的目标2， 肥胖和瘦身大鼠对高脂肪和高碳水化合物的差异特征 大鼠的饮食；3)特定目标3，慢性刺激与 Gal或NPY会导致暴饮暴食并增加身体脂肪；4)特定目标4， 不同倾向性正常体重大鼠的神经肽功能 高脂饮食下的肥胖；5)特定目标5，急性多肽的影响 注射影响体内脂肪积累的内分泌和代谢系统；6) 特定目标6，潜在变化的神经内分泌和代谢机制 富含脂肪或碳水化合物的食物中的多肽；7)特定目标 7、肥胖大鼠肥胖后胰岛素升高的神经肽特征 8)特定目标8)近交系小鼠不同品系 饮食模式和体重增加。这项研究的总体目标是 除了定义GAL和NPY的功能作用外，还将建立一个 使用不同的动物模型、实验策略和 可能拓宽我们对大脑功能的视角的多学科技术 因为它关系到能量平衡。

DESCRIPTION (adapted from applicant's abstract): Obesity is pervasive and growing in industrialized societies. One important factor known to contribute to this increase is the availability of high-fat or high-calorie diets. Another factor to consider is individual predisposition to weight gain, due to genetic or early environmental influences. The goal of this research is to use innovative approaches to examine the role of brain peptides in relation to diet and predisposition. These neurochemicals are galanin (GAL) and neuropeptide Y (NPY), which in the hypothalamus are known to stimulate eating behavior and reduce energy expenditure but whose specific roles in obesity still remain to be elucidated. One main objective of this research is to determine whether, in models of dietary obesity that mimic the human condition, these peptides have a causal relationship to disturbances in eating and body weight control. Specifically, it is hypothesized that: a) GAL, in specific neurons of the paraventricular nucleus (PVN) that project to the median eminence (ME), contributes to increased body weight gain and adiposity in response to a high-fat diet; and b) NPY, in neurons of the arcuate nucleus (ARC) that project to the PVN, induces weight gain in response to a high-calorie diet with excess carbohydrate. This research program has been broadened to include new experimental models and techniques; simultaneous analyses of behavioral, endocrine, metabolic and neurochemical parameters; and studies of different animal populations. The proposed experiments will investigate, in: 1) Specific Aim 1, changes in neurobiological and metabolic systems induced by overeating of high-fat or high-carbohydrate diets in rats; 2) Specific Aim 2, the differential traits of obese and lean rats on high-fat or high-carbohydrate diets in rats; 3) Specific Aim 3, conditions in which chronic stimulation with GAL or NPY induces overeating and increases body fat; 4) Specific Aim 4, neuropeptide function in normal-weight rats with differential propensity toward obesity on a high-fat diet; 5) Specific Aim 5, effects of acute peptide injection on endocrine and metabolic systems that affect body fat accrual; 6) Specific Aim 6, the neuroendocrine and metabolic mechanisms underlying changes in peptides in response to fat-rich or carbohydrate-rich meals; 7) Specific Aim 7, neuropeptide traits in obesity-prone rats with higher insulin after a high-fat meal; and 8) Specific Aim 8, inbred mouse strains with different patterns of eating and weight gain. The overall objective of this research, in addition to defining the functional role of GAL and NPY, is to establish a program with different animal models, experimental strategies and multidisciplinary techniques that may broaden our perspective of brain function as it relates to energy balance.