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）：肥胖和相关的代谢障碍已成为一个重大的公共卫生问题，过度消费非常可口的热量浓密食物是一个促成因素。该提案调查了将食物的奖励价值与肠道衍生的饱腹感和饱腹感信号的投入整合在一起的神经回路，并将解决这些电路以控制食物摄入量的生理相关性。我们建议，饱腹感信号传导的大脑介导涉及食物的奖励价值下降，相反，预测高度奖励食物的提示会抑制大脑内的饱腹感。此处提出的实验将检查我们认为与这些相互作用有关的两个电路：1）胰高血糖素样肽1（GLP-1）投影从孤立区的后脑核（NTS）核（NTS）到前脑核的核心核心（NACC），已知的领域，在食物奖励中起重要作用； 2）Orexin-A（ORXA）从下丘脑（LH）到NTS的投影，这对于检测和对饱腹和饱腹感信号的反应至关重要。我们实验室的最新数据表明，NACC中的GLP-1作用会降低食物摄入量，并可能有助于营养诱导的饱腹感。我们将对NACC GLP-1激动剂和拮抗剂治疗的粉状模式效应进行详细分析，并检查NACC投射GLP-1神经元是否通过与进餐相关的胃肠道信号激活了NACC，以确定GLP-1对NACC的投影是否介导了NACC介导的餐食诱发的餐食或大鼠中的饱食。接下来，我们将评估NACC中GLP-1的作用是降低食品可口性还是大鼠获得食物的动力。我们假设ORXA对NTS的投影的功能相反。这些神经元被预测高度有益食物的提示激活，我们有新的证据表明后脑Orxa治疗可以通过损害满足来增加食物摄入量。在这里，我们将研究内源性ORXA作用在后脑脑中的作用在营养诱发的饱腹感和饱腹感中，食物动机的操作行为以及对预测高度可口食品可用性的提示的行为反应。我们认为，对奖励和满足/饱腹感如何在大脑中相互作用的了解最终将导致新的候选者治疗肥胖和暴饮暴食，从而更有效地针对这些疾病所涉及的特定功能失调的行为。