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R01 Application:Genetically Dissecting Cholinergic Signaling in Body Weight Control.

R01 应用：体重控制中的胆碱能信号传导的基因剖析。

基本信息

批准号：
9754134
负责人：
Benjamin R Arenkiel
金额：
$ 35.4万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-15 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9754134
关键词：
Ablation Acetylcholine Affect Animal Behavior Behavior Behavioral Body Weight Brain Brain region Cardiovascular Diseases Cause of Death Cells Complex Data Desire for food Development Diabetes Mellitus Diagonal Band of Broca Eating Electrophysiology (science)Energy Metabolism Exhibits Feeding behaviors Genetic Goals Homeostasis Human Hyperphagia Hypothalamic structure Individual Knowledge Maps Mediating Metabolic Metabolism Morbid Obesity Mutagenesis Neural Pathways Neuraxis Neurons Neurotransmitters Obesity Obesity associated disease Pathway interactions Pattern Pharmaceutical Preparations Physiological Physiology Play Population Process Prosencephalon Regulation Research Rodent Role Satiation Signal Pathway Signal Transduction Smoking Synapses Testing Treatment Efficacy United States Weight Gain Weight maintenance regimen basal forebrain cellular targeting cholinergic cholinergic neuron experimental study feeding gamma-Aminobutyric Acid hindbrain insight molecular marker neural circuit neuroregulation novel nutrient metabolism obesity development optogenetics postsynaptic programs relating to nervous system side effect smoking cessation therapeutic development

项目摘要

Abstract/Project Summary Obesity-associated diseases such as diabetes and cardiovascular disease together account for the leading cause of death in the United States. Roughly one-third of the U.S. population is obese, and it is estimated that nearly half of the population will be obese within the next two decades. To date, studies investigating the neural contribution to body weight control have focused largely on neuropeptidergic signaling in the hypothalamus, a key brain region involved in feeding behavior. However, signaling from extra-hypothalamic brain regions has also been implicated in regulating nutrient metabolism, appetite, and satiety. We recently uncovered a novel mechanism by which cholinergic signaling in the basal forebrain strongly influences body weight control. This discovery provides intriguing evidence that specific cholinergic signaling pathways in the brain critically regulate feeding behavior and body weight homeostasis. To elucidate the mechanisms by which forebrain cholinergic signaling influences body weight management, feeding behaviors, and metabolism, we will test the hypothesis that cholinergic signaling modulates metabolic and appetitive programs to regulate body weight. Using a combination conditional genetic targeting, optogenetic manipulations, electrophysiology, and behavioral analysis, we will set out to determine the role for basal forebrain cholinergic signaling in body weight control and obesity.

摘要/项目摘要与肥胖相关的疾病，如糖尿病和心血管疾病，美国的死因。大约有三分之一的美国人口肥胖，据估计，近一半的人口将在未来二十年内肥胖。迄今为止，研究神经对体重控制的贡献主要集中在神经肽能信号传导上，下丘脑，一个与进食行为有关的关键大脑区域。然而，来自下丘脑外的信号大脑区域也与调节营养代谢、食欲和饱腹感有关。我们最近揭示了一种新的机制，通过这种机制，基底前脑中的胆碱能信号强烈影响身体体重控制这一发现提供了有趣的证据，表明特定的胆碱能信号通路，大脑严格地调节进食行为和体重动态平衡。为了阐明前脑胆碱能信号影响体重管理、摄食行为和代谢，我们将测试胆碱能信号调节代谢和食欲程序的假设，体重使用条件遗传靶向、光遗传学操作、电生理学，和行为分析，我们将着手确定基底前脑胆碱能信号在体内的作用，体重控制和肥胖。