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Behavioral Physiology of Body Weight Regulation

体重调节的行为生理学

基本信息

批准号：
8450864
负责人：
DIANNE FIGLEWICZ LATTEMANN
金额：
$ 26.9万
依托单位：
SEATTLE INST FOR BIOMEDICAL/CLINICAL RES
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-09-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8450864
关键词：
Abstinence Address Adipose tissue Adolescent Adult Age Animal Model Animals Area Behavior Behavior Therapy Behavioral Behavioral Paradigm Beta Cell Biochemical Body Weight Brain Brain region Cell Nucleus Childhood Chronic Data Development Diabetes Mellitus Diet Diet Habits Dose Eating Effectiveness Endocrine Energy Intake Exhibits Exposure to FOS gene Fatty acid glycerol esters Feedback Food Goals Homeostasis Hormones Human Hypothalamic structure Incidence Injection of therapeutic agent Insulin Insulin Resistance Intake Intervention Lead Leptin Measures Medial Mediating Metabolic Middle Hypothalamus Modeling Motivation Neurons Neurosecretory Systems Nucleus Accumbens Nutritional status Obesity Pathway interactions Pattern Performance Phenotype Physiology Population Prevalence Progress Reports Puberty Public Health Rattus Regulation Relapse Resistance Rewards Role STAT3 gene Secondary to Self Administration Severities Signal Pathway Signal Transduction Site Societies Solutions Structure of nucleus infundibularis hypothalami Sucrose Synapses Testing Therapeutic Intervention Time Validation Ventral Tegmental Area base brain cell craving density energy density experience feeding indexing inhibitor/antagonist insight insulin signaling islet juvenile animal novel preference public health relevance recidivism research study response reward circuitry sugar sweet taste perception sweetened beverage young adult

项目摘要

DESCRIPTION (provided by applicant): The contribution of non-homeostatic factors to the recent increase of obesity incidence in Westernized populations such as the U.S., has now come to be appreciated. Ready availability and affordability of palatable, high caloric density foods; activation of responsive CNS pathways that mediate motivation and reward; and loss of effectiveness of endocrine adiposity signals to act at the CNS, may all contribute to excess caloric intake. Our lab has focused on the potential role of the candidate adiposity signals insulin and leptin to modulate 'food reward behavior'. Insulin and leptin act at the medial hypothalamus to regulate energy homeostasis; they also act at CNS sites that mediate reward and motivation. Both decrease performance in behavioral tasks which assess food reward. This occurs at doses that are subthreshold for effects on long-term energy homeostasis, which suggests that the reward-suppressive effects of insulin and leptin are independent of their chronic effects to decrease food intake and regulate body weight. Our recent studies demonstrate that both the medial hypothalamic arcuate nucleus (ARC) and the ventral tegmental area (VTA) are direct sites of action for insulin and leptin to inhibit food reward; and that the effectiveness of insulin and leptin is reversed by high fat diet background. These new insights lead to new questions which will be addressed by pursuing the Specific Aims summarized below. These Aims will evaluate anatomical, behavioral, and developmental aspects of food reward modulation by insulin and leptin. The long-term objective is to delineate the behavioral and synaptic mechanisms that modulate food reward, in relationship to diet or nutritional status. The current Aims will build towards that objective by evaluating: 1) the ability of insulin, leptin, or cell signaling inhibitors to modulate performance in a behavioral task that models diet recidivism, relapse to sucrose-seeking; 2) the effect of high fat diet experience on sucrose self-administration in pre- and post-pubertal rats; and 3) the CNS sites activated in response to sucrose self-administration and modulation of this activation by insulin, leptin, or cell-signaling inhibitors. These studies will elucidate key brain regions and cell signaling pathways which modulate food reward and are targets for insulin and leptin. This could provide the basis for potential therapeutic intervention strategies targeting non-homeostatic, 'reward-based' feeding, a public health problem that is relevant for both adult and pediatric populations in the U.S.

描述（由申请人提供）：非体内平衡因素对最近在美国等西方化人群中肥胖发病率增加的贡献，现在已经得到了重视。美味的、高热量密度的食物唾手可得、价格可承受；介导动机和奖励的反应性中枢神经系统通路的激活；以及内分泌肥胖信号作用于中枢神经系统的有效性丧失，都可能导致过量的热量摄入。我们的实验室一直专注于研究候选肥胖信号胰岛素和瘦素在调节“食物奖励行为”中的潜在作用。胰岛素和瘦素作用于下丘脑内侧调节能量稳态；它们也在中枢神经系统中调节奖励和动机。两者都会降低评估食物奖励的行为任务的表现。这种情况发生在对长期能量稳态影响的阈值以下，这表明胰岛素和瘦素的奖励抑制作用独立于它们减少食物摄入和调节体重的慢性作用。我们最近的研究表明，下丘脑内侧弓状核（ARC）和腹侧被盖区（VTA）是胰岛素和瘦素抑制食物奖励的直接作用部位；胰岛素和瘦素的有效性会被高脂肪饮食背景所逆转。这些新的见解导致了新的问题，这些问题将通过追求下面总结的具体目标来解决。这些目的将评估胰岛素和瘦素对食物奖励调节的解剖学、行为学和发育方面的影响。长期目标是描述调节食物奖励的行为和突触机制，与饮食或营养状况有关。当前Aims将通过评估来实现这一目标：1)胰岛素、瘦素或细胞信号抑制剂在模拟饮食累犯、重新寻求蔗糖的行为任务中调节表现的能力；2)高脂饮食经历对青春期前后大鼠蔗糖自我给药的影响；3)中枢神经系统部位对蔗糖自我给药的反应以及胰岛素、瘦素或细胞信号传导抑制剂对这种激活的调节。这些研究将阐明调节食物奖励的关键大脑区域和细胞信号通路，它们是胰岛素和瘦素的靶点。这可以为潜在的治疗干预策略提供基础，针对非稳态，“基于奖励的”喂养，这是一个与美国成人和儿科人口相关的公共卫生问题