HYPOTHALAMIC NEUROTRANSMITTER SYSTEMS & EATING BEHAVIOR

描述（改编自申请人的摘要）：肥胖是普遍的， 在工业化社会中成长。一个重要的因素是 高脂肪或高热量饮食的可获得性是导致这种增加的原因。另一 要考虑的因素是个人倾向于体重增加，由于遗传 或早期环境的影响。这项研究的目的是利用 研究脑肽与饮食关系的创新方法 和易感性这些神经化学物质是甘丙肽（GAL）和神经肽Y (NPY)，下丘脑中的这种物质可以刺激进食行为， 减少能量消耗，但其在肥胖中的具体作用仍然存在， 被阐明。这项研究的一个主要目标是确定， 在模拟人类状况的饮食性肥胖模型中，这些肽具有 与进食和体重控制障碍的因果关系。 具体而言，假设：a）GAL，在特定的神经元中， 室旁核（PVN）投射到正中隆起（ME）， 有助于增加体重增加和肥胖， 高脂饮食;和B）在投射到神经元的弓状核（ARC）的神经元中的NPY PVN，诱导体重增加，以响应高热量饮食， 糖类。这项研究计划已扩大到包括新的 实验模型和技术;同时分析行为， 内分泌、代谢和神经化学参数;以及不同 动物种群。拟议的实验将调查，在：1）具体 目的1，暴饮暴食引起的神经生物学和代谢系统的变化 高脂肪或高碳水化合物饮食的大鼠; 2）具体目标2， 肥胖和瘦型大鼠在高脂或高碳水化合物条件下的差异性状 3）具体目标3，慢性刺激条件下， GAL或NPY诱导暴饮暴食并增加体脂肪; 4）特定目标4， 正常体重大鼠的神经肽功能， 高脂饮食的肥胖症; 5）具体目标5，急性肽的作用 注射对内分泌和代谢系统影响身体脂肪积累; 6） 具体目标6，变化背后的神经内分泌和代谢机制 在肽中响应富含脂肪或碳水化合物的膳食; 7）具体目标 7、神经肽性状在肥胖倾向大鼠中具有较高的胰岛素后， 高脂肪膳食;和8）特定目标8，具有不同 饮食模式和体重增加。本研究的总体目标是， 除了确定GAL和NPY的功能作用外，还建立了一个 不同的动物模型，实验策略和 多学科技术，可以拓宽我们对大脑功能的看法， 因为它与能量平衡有关。

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.