Neuroendocrine Integration of Satiety and Food Reward

饱腹感和食物奖励的神经内分泌整合

基本信息

  • 批准号:
    8503884
  • 负责人:
  • 金额:
    $ 30.72万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 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

项目摘要

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(申请人提供):肥胖和相关的代谢障碍已经成为一个重要的公共健康问题,过度消费高可口的高热量食物是一个促成因素。这项建议研究了将食物的奖励价值与来自肠道来源的饱腹感和饱腹感信号的输入相结合的神经回路,并将解决这些回路与控制食物摄入量的生理相关性。我们认为,大脑对饱腹感信号的调节涉及食物奖励价值的降低,相反,预测高回报食物的线索可以抑制大脑中的饱腹感信号。这里提出的实验将研究我们认为参与这些相互作用的两个回路:1)从孤束后脑核(NTS)到前脑伏隔核(NACC)的胰高血糖素样肽1(GLP-1)投射,已知在食物奖赏中发挥重要作用;以及2)从下丘脑外侧(LH)到NTS的食欲素-A(OrxA)投射,这是检测和响应饱和饱信号的关键区域。来自我们实验室的最新数据表明,GLP-1在NACC中的作用减少了食物的摄入量,并可能有助于营养诱导的饱腹感。我们将详细分析NACC内GLP-1激动剂和拮抗剂治疗对进食模式的影响,并检查投射NACC的GLP-1神经元是否被与进食相关的胃肠道信号激活,以确定投射到NACC的GLP-1是否介导了进食诱导的饱足感。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取食物的动机。我们假设OrxA向NTS的投射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量。在这里,我们将研究内源性OrxA在后脑中的作用,在营养诱导的饱腹感、食物动机的操控行为中的作用,以及对预测高度美味食物可用性的提示的行为反应。我们相信,对奖赏和饱腹感/饱腹感在大脑中如何相互作用的更好理解,最终将导致治疗肥胖和暴饮暴食的新候选药物,从而更有效地针对与这些疾病相关的特定功能障碍行为。

项目成果

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Diana L Williams其他文献

Diana L Williams的其他文献

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{{ truncateString('Diana L Williams', 18)}}的其他基金

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:
    8820912
  • 财政年份:
    2013
  • 资助金额:
    $ 30.72万
  • 项目类别:
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:
    10359770
  • 财政年份:
    2013
  • 资助金额:
    $ 30.72万
  • 项目类别:
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:
    8631083
  • 财政年份:
    2013
  • 资助金额:
    $ 30.72万
  • 项目类别:
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:
    9020224
  • 财政年份:
    2013
  • 资助金额:
    $ 30.72万
  • 项目类别:
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:
    9234527
  • 财政年份:
    2013
  • 资助金额:
    $ 30.72万
  • 项目类别:
Brain integration of adiposity and satiety signals in the control of food intake
大脑整合肥胖和饱腹感信号来控制食物摄入
  • 批准号:
    8139452
  • 财政年份:
    2007
  • 资助金额:
    $ 30.72万
  • 项目类别:
Brain integration of adiposity and satiety signals in the control of food intake
大脑整合肥胖和饱腹感信号来控制食物摄入
  • 批准号:
    7903217
  • 财政年份:
    2007
  • 资助金额:
    $ 30.72万
  • 项目类别:
Brain integration of adiposity and satiety signals in the control of food intake
大脑整合肥胖和饱腹感信号来控制食物摄入
  • 批准号:
    7300935
  • 财政年份:
    2007
  • 资助金额:
    $ 30.72万
  • 项目类别:
Brain integration of adiposity and satiety signals in the control of food intake
大脑整合肥胖和饱腹感信号来控制食物摄入
  • 批准号:
    7487316
  • 财政年份:
    2007
  • 资助金额:
    $ 30.72万
  • 项目类别:
Brain integration of adiposity and satiety signals in the control of food intake
大脑整合肥胖和饱腹感信号来控制食物摄入
  • 批准号:
    8119759
  • 财政年份:
    2007
  • 资助金额:
    $ 30.72万
  • 项目类别:

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