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：
9316604
负责人：
Benjamin R Arenkiel
金额：
$ 35.41万
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/9316604
关键词：
Ablation Acetylcholine Adverse effects 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 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 drug development experimental study feeding gamma-Aminobutyric Acid hindbrain insight molecular marker neural circuit neuroregulation novel nutrient metabolism optogenetics postsynaptic programs relating to nervous system 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/项目摘要糖尿病和心血管疾病等与肥胖相关的疾病共同占主导地位美国的死因。大约三分之一的美国人口患有肥胖症，据估计近一半的人口将在未来二十年内肥胖。迄今为止，研究调查了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，参与进食行为的关键大脑区域。然而，来自下丘脑外的信号大脑区域还与调节营养代谢、食欲和饱腹感有关。我们最近发现了一种新机制，通过该机制，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调节进食行为和体重稳态。阐明其机制前脑胆碱能信号影响体重管理、进食行为和新陈代谢，我们将检验胆碱能信号调节代谢和食欲程序以调节的假设体重。结合使用条件遗传靶向、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。