Neuroendocrine Integration of Satiety and Food Reward

饱腹感和食物奖励的神经内分泌整合

• 批准号: 8503884
• 负责人: Diana L Williams
• 金额: $ 30.72万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8503884
• 关键词: Address; Affect; Agonist; Area; Association Learning; Attention; Attenuated; Behavior; Behavioral; Biological Factors; Body Weight; Brain; Brain Stem; Brain region; Canned Foods; Clinical Treatment; Consumption; Cues; Data; Detection; Development; Disease; Eating; Evaluation; Feeding behaviors; Feeling; Food; Frequencies; Functional disorder; Gastrointestinal tract structure; Human; Hyperphagia; Hypothalamic structure; Injection of therapeutic agent; Insulin; Laboratories; Lateral; Lead; Leptin; Link; Maintenance; Mediating; Mediation; Metabolic Diseases; Modeling; Motivation; Neurons; Neuropeptides; Neurosecretory Systems; Nucleus Accumbens; Nucleus solitarius; Nutrient; Obesity; Pattern; Performance; Physiological; Play; Process; Prosencephalon; Psychological reinforcement; Public Health; Rattus; Receptor Activation; Research; Rewards; Role; Satiation; Schedule; Signal Transduction; Stimulus; Stomach; Sucrose; System; Taste Perception; Ventral Tegmental Area; base; brain pathway; feeding; gastrointestinal; glucagon-like peptide; glucagon-like peptide 1; hedonic; hindbrain; improved; mind control; motivated behavior; neural circuit; obesity treatment; orexin 1 receptor; orexin A; preference; public health relevance; receptor; research study; response

DESCRIPTION (provided by applicant): Obesity and related metabolic disorders have become a significant public health problem, and overconsumption of highly palatable calorically dense food is a contributing factor. This proposal investigates the neural circuitry that integrate the rewarding value of food with input from gut-derived satiation and satiety signals, and will address the physiological relevance of these circuits for the control of food intake. We propose that brain mediation of satiety signaling involves a decrease in the rewarding value of food, and that conversely, cues predicting highly rewarding food can dampen satiety signaling within the brain. The experiments proposed here will examine two of the circuits that we believe to be involved in these interactions: 1) the glucagon-like peptide 1 (GLP-1) projection from the hindbrain nucleus of the solitary tract (NTS) to the forebrain nucleus accumbens core (NAcC), an area known to plays an important role in food reward; and 2) the Orexin-A (OrxA) projection from the lateral hypothalamus (LH) to the NTS, an area critical for the detection of and response to satiation and satiety signals. Recent data from our laboratory suggests that GLP-1 action in NAcC reduces food intake and may contribute to nutrient-induced satiety. We will apply detailed analysis of the meal pattern effects of intra-NAcC GLP-1 agonist and antagonist treatment, and examine whether NAcC- projecting GLP-1 neurons are activated by meal-related gastrointestinal signals in order to determine whether the GLP-1 projection to NAcC mediates meal-induced satiation or satiety in rats. Next, we will evaluate whether GLP-1 action in NAcC reduces food palatability or rats' motivation to obtain food. We hypothesize that the OrxA projection to NTS functions in the opposite manner. These neurons are activated by cues that predict highly rewarding food, and we have new evidence that hindbrain OrxA treatment can increase food intake by impairing satiation. Here we will investigate the role of endogenous OrxA action in the hindbrain in nutrient- induced satiation and satiety, food-motivated operant behavior, and the behavioral response to cues that predict the availability of highly palatable food. We believe that improved understanding of how reward and satiation/satiety interact within the brain will ultimately lead to new candidates for treatment of obesity and overeating that more effectively target the specific dysfunctional behaviors involved in these disorders.

描述（由申请人提供）：肥胖和相关代谢紊乱已成为一个重大的公共卫生问题，过度食用高可口的热量密集的食物是一个促成因素。这项建议调查的神经回路，整合奖励价值的食物与输入来自肠道的饱足感和饱足感信号，并将解决这些电路的生理相关性的控制食物的摄入量。我们提出，大脑调解的饱腹感信号涉及减少奖励价值的食物，相反，线索预测高度奖励的食物可以抑制大脑内的饱腹感信号。本实验将研究我们认为参与这些相互作用的两个回路：1）胰高血糖素样肽1（GLP-1）从孤束核（NTS）到前脑核团（NAcC）的投射，该区域已知在食物奖励中起重要作用;和2）食欲素-A（OrxA）从外侧下丘脑（LH）到NTS的投射，NTS是检测和响应饱足和饱足信号的关键区域。我们实验室的最新数据表明，NAcC中的GLP-1作用减少了食物摄入，并可能导致营养诱导的饱腹感。我们将对NAcC内GLP-1激动剂和拮抗剂治疗的进餐模式效应进行详细分析，并检查NAcC投射GLP-1神经元是否被进餐相关胃肠道信号激活，以确定GLP-1向NAcC的投射是否介导大鼠中进餐诱导的饱足感或饱食感。接下来，我们将评估GLP-1在NAcC中的作用是否会降低食物的适口性或大鼠获得食物的动机。我们假设OrxA投射到NTS以相反的方式起作用。这些神经元被预测高回报食物的线索激活，我们有新的证据表明，后脑OrxA治疗可以通过削弱饱腹感来增加食物摄入。在这里，我们将研究内源性OrxA行动在营养诱导的饱足感和饱足感，食物动机的操作行为，和行为反应的线索，预测高度可口的食物的可用性在后脑中的作用。我们相信，更好地理解奖励和饱腹感/饱腹感如何在大脑中相互作用，最终将导致治疗肥胖和暴饮暴食的新候选人，更有效地针对这些疾病中涉及的特定功能失调行为。