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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.

抽象/项目总结