HYPOTHALAMIC NEUROTRANSMITTER SYSTEMS & EATING BEHAVIOR

下丘脑神经递质系统

• 批准号: 6751316
• 负责人: SARAH F LEIBOWITZ
• 金额: $ 33.4万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6751316
• 关键词: adipose tissue; albino rat; appetite regulatory center; behavioral /social science research tag; bioenergetics; dietary carbohydrates; dietary excess; dietary lipid; disease /disorder proneness /risk; galanin; genetic strain; genetic susceptibility; hormone regulation /control mechanism; hypothalamic hormones; inbreeding; injection /infusion; insulin; laboratory mouse; neuroendocrine system; neuropeptide Y; neuropsychology; neurotransmitters; nutrition related tag; overeating; phenotype; weight gain

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.

描述（改编自申请人的摘要）：肥胖是普遍存在的，并且 在工业化社会中成长。已知的一个重要因素 导致这一增长的原因是高脂肪或高热量饮食的可获得性。其他 需要考虑的因素是由于遗传因素导致的个体体重增加倾向 或早期环境影响。这项研究的目标是利用 检查脑肽与饮食关系的作用的创新方法 和倾向。这些神经化学物质是甘丙肽 (GAL) 和神经肽 Y （NPY），已知它在下丘脑中可以刺激饮食行为 减少能量消耗，但其在肥胖中的具体作用仍有待确定 予以阐明。这项研究的一个主要目标是确定是否 模拟人类状况的饮食肥胖模型，这些肽具有 与饮食和体重控制障碍之间的因果关系。 具体来说，假设： a) GAL，在特定神经元中 室旁核（PVN）投射到正中隆起（ME）， 有助于增加体重增加和肥胖 高脂肪饮食； b) NPY，位于弓状核 (ARC) 的神经元中，投射 PVN，由于高热量饮食和过量摄入而导致体重增加 糖类。该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；以及不同的研究 动物种群。拟议的实验将研究以下方面：1）具体 目标1、暴饮暴食引起的神经生物学和代谢系统的变化 大鼠的高脂肪或高碳水化合物饮食； 2) 具体目标 2， 肥胖和瘦大鼠对高脂肪或高碳水化合物的差异特征 大鼠的饮食； 3) 具体目标3，慢性刺激的条件 GAL或NPY诱发暴饮暴食，增加体内脂肪； 4) 具体目标 4, 具有不同倾向的正常体重大鼠的神经肽功能 高脂肪饮食导致肥胖； 5) 具体目标5、急性肽的作用 注射影响身体脂肪累积的内分泌和代谢系统； 6） 具体目标6，神经内分泌和代谢机制潜在的变化 含有肽以响应富含脂肪或富含碳水化合物的膳食； 7) 具体目标 图7，具有较高胰岛素水平的肥胖倾向大鼠的神经肽特征 高脂肪膳食； 8) 具体目标 8，具有不同特征的近交系小鼠品系 饮食模式和体重增加。本研究的总体目标是 除了定义 GAL 和 NPY 的功能角色外，还需要建立一个 不同动物模型、实验策略和 多学科技术可以拓宽我们对大脑功能的认识 因为它与能量平衡有关。

项目成果

Glucocorticoid receptors in PVN: interactions with NE, NPY, and Gal in relation to feeding.

PVN 中的糖皮质激素受体：与进食相关的 NE、NPY 和 Gal 的相互作用。

• DOI: 10.1152/ajpendo.1993.265.5.e794
• 发表时间: 1993
• 期刊: The American journal of physiology
• 作者: Tempel,DL;Leibowitz,SF
• 通讯作者: Leibowitz,SF

Hypothalamic neuropeptide Y in relation to energy balance.

下丘脑神经肽 Y 与能量平衡的关系。

• DOI: 10.1111/j.1749-6632.1990.tb48939.x
• 发表时间: 1990
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Leibowitz,SF

Obesity on a high-fat diet: role of hypothalamic galanin in neurons of the anterior paraventricular nucleus projecting to the median eminence.

高脂肪饮食导致的肥胖：下丘脑甘丙肽在投射到正中隆起的前室旁核神经元中的作用。

• DOI: 10.1523/jneurosci.18-07-02709.1998
• 发表时间: 1998
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Leibowitz,SF;Akabayashi,A;Wang,J
• 通讯作者: Wang,J

Impact of a galanin antagonist on exogenous galanin and natural patterns of fat ingestion.

甘丙肽拮抗剂对外源性甘丙肽和脂肪摄入自然模式的影响。

• DOI: 10.1016/0006-8993(92)90863-5
• 发表时间: 1992
• 期刊: Brain research
• 影响因子: 2.9
• 作者: Leibowitz,SF;Kim,T
• 通讯作者: Kim,T

Leptin secretion after a high-fat meal in normal-weight rats: strong predictor of long-term body fat accrual on a high-fat diet.

正常体重大鼠高脂肪膳食后瘦素的分泌：高脂肪饮食长期体内脂肪累积的有力预测因子。

• DOI: 10.1152/ajpendo.00609.2004
• 发表时间: 2006
• 期刊: American journal of physiology. Endocrinology and metabolism.
• 作者: Leibowitz,SF;Chang,G-Q;Dourmashkin,JT;Yun,R;Julien,C;Pamy,PP
• 通讯作者: Pamy,PP