Genetically Dissecting Chorinergic Signaling in Body Weight Control

从基因角度剖析体重控制中的胆碱能信号

基本信息

批准号：
10259773
负责人：
Benjamin R Arenkiel
金额：
$ 45.54万
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 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10259773
关键词：
Acute Address Affect Anatomy Area Attention Award Behavior Behavioral Body Weight Brain Brain region Cardiovascular Diseases Cause of Death Chronic Data Desire for food Diabetes Mellitus Diagonal Band of Broca Diet Diet Habits Eating Eating Behavior Electrophysiology (science)Fasting Feeding behaviors Food Food Aversion Genetic Glutamates Goals Habenula Healthy Eating Homeostasis Hyperphagia Hypothalamic structure Knowledge Lateral Life Link Mediating Mental Depression Metabolic Metabolism Nature Neuraxis Neurons Obesity Obesity associated disease Population Prosencephalon Research Proposals Research Support Rewards Role Satiation Sensory Signal Pathway Signal Transduction Starvation Synapses Testing United States Wakefulness Weight maintenance regimen addiction basal forebrain basal forebrain cholinergic neurons base cell type cholinergic cholinergic neuron energy balance experimental study feeding food consumption glutamatergic signaling insight neurotransmission novel nutrient metabolism obesity development optogenetics programs relating to nervous system reward processing

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 have recently uncovered a novel mechanism by which glutamatergic signaling in the basal forebrain strongly influences feeding and body weight control. This discovery provides intriguing evidence that specific glutamatergic signaling pathways in the brain critically regulate feeding behavior and body weight homeostasis. To elucidate the mechanisms by which forebrain glutamatergic signaling influences body weight management, feeding behaviors, and metabolism, we will test the hypothesis that glutamatergic basal forebrain circuits modulate 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 glutamatergic signaling in body weight control and obesity.

摘要/项目摘要肥胖相关疾病，例如糖尿病和心血管疾病，共同考虑了领先的美国死亡原因。大约三分之一的美国人口肥胖，据估计在接下来的二十年中，将近一半的人口将肥胖。迄今为止，研究神经对体重控制的贡献主要集中在下丘脑中的神经肽智信号传导上涉及进食行为的关键大脑区域。但是，来自亚型丘脑大脑区域的信号传导具有还与调节营养代谢，食欲和饱腹感有关。我们最近发现了基础前脑中谷氨酸能信号传导强烈影响喂养和身体的新型机制体重控制。这一发现提供了有趣的证据，表明特定的谷氨酸能信号传导途径大脑严重调节喂养行为和体重稳态。阐明该机制前脑谷氨酸能信号传导影响体重管理，喂养行为和代谢，我们将检验以下假设：谷氨酸能基础前脑电路调节代谢和食欲调节体重。使用有条件的遗传靶向，光遗传操作，电生理学和行为分析，我们将着手确定基础前脑谷氨酸能的作用体重控制和肥胖中的信号传导。