CNS Mechanisms Linking Exercise Training with Energy Balance and Metabolism

将运动训练与能量平衡和新陈代谢联系起来的中枢神经系统机制

• 批准号: 10677755
• 负责人: JOEL K. ELMQUIST
• 金额: $ 191.92万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10677755
• 关键词: Animal Model; Behavioral; Body Composition; Brain; Cell Nucleus; Central Nervous System; Communication; Disease; Eating; Electrophysiology (science); Energy Metabolism; Exercise; Genetic; Glutamates; Goals; Grant; Histologic; Histology; Hormones; Hypertension; Hypothalamic structure; Individual; Injections; Laboratories; Laboratory Finding; Link; Liver; Malignant Neoplasms; Maps; Mediating; Metabolic; Metabolism; Modeling; Molecular; Mus; Neuroanatomy; Neurons; Non-Insulin-Dependent Diabetes Mellitus; Nuclear Receptors; Obesity; Organ; Peptides; Peripheral; Physiological; Plasma; Pro-Opiomelanocortin; Property; Protocols documentation; Regulation; Research Design; Research Personnel; Rhodopsin; Role; SF1; Series; Services; Signal Transduction; Standardization; Synapses; System; Testing; Tissues; Training; Validation; blood glucose regulation; endurance exercise; energy balance; exercise training; experimental study; feeding; ghrelin; glucagon-like peptide 1; human subject; improved; innovation; insight; insulin sensitivity; metabolic phenotype; mouse model; multidisciplinary; neuronal circuitry; neurotransmission; physical inactivity; predictive modeling; programs; response; tool

ABSTRACT We have assembled a multidisciplinary team of investigators to investigate how the brain and key peripheral metabolic signals regulate feeding and glucose homeostasis following exercise. In particular, we have developed a program focused on using unique, genetic mouse models to understand why exercise training improves multiple metabolic parameters including insulin sensitivity and changes in body composition. We propose a set of projects that revolve around the hypothesis that several of these exercise-associated effects are mediated by changes in key brain circuits. The investigators involved in this application, Elmquist, Betley Zigman, and Williams bring distinct and synergistic expertise to the table. The Elmquist/Betley group will investigate the role of the ventromedial hypothalamus nucleus (VMH) neurons in the regulation of metabolic changes induced by exercise. The Zigman group will investigate the physiological importance of ghrelin signaling in regulating responses to exercise. The Williams group will investigate the changes in fundamental cellular properties of hypothalamic neurons following exercise training These three tightly interwoven Projects will address a number of new aspects of inter-organ communication between the peripheral tissues and critical regions in the brain. Three Cores will support the three Projects in these efforts: A) Administrative Core; B) Mouse Exercise and Metabolic Phenotyping Core and the C) Neuroanatomy/Histology/Brain Injection Core. In summary, these innovative and synergistic studies will increase the understanding of how exercise training regulates key peripheral metabolic signals via changes in central nervous system circuits.

摘要 我们已经组建了一个多学科的调查小组，以调查大脑和关键的外围设备是如何被破坏的。 代谢信号调节运动后的进食和葡萄糖稳态。我们特别 开发了一个项目，专注于使用独特的遗传小鼠模型来了解为什么运动训练 改善多种代谢参数，包括胰岛素敏感性和身体成分的变化。我们 提出了一系列围绕以下假设的项目：其中一些与运动相关的影响 都是由关键脑回路的变化来调节的。参与这项申请的调查人员埃尔姆奎斯特、贝特利 齐格曼和威廉姆斯带来了独特的和协同的专业知识表。Elmquist/Betley集团将 探讨下丘脑腹内侧核（VMH）神经元在代谢调节中的作用， 运动引起的变化。齐格曼小组将研究生长激素释放肽的生理重要性 调节运动反应的信号。威廉姆斯小组将研究基本面的变化， 运动训练后下丘脑神经元的细胞特性这三个紧密交织的项目 将解决一些新的方面的器官间通讯之间的外周组织和关键 大脑中的区域。三个核心将在这些方面支持三个项目：A）行政核心; B） 小鼠运动和代谢表型核心和C）神经解剖学/组织学/脑注射 核心总之，这些创新和协同研究将增加对运动如何 训练通过中枢神经系统回路的变化来调节关键的外周代谢信号。

项目成果

Leptin-inhibited neurons in the lateral parabrachial nucleus do not alter food intake or glucose balance.

• DOI: 10.1080/19768354.2022.2084159
• 发表时间: 2022
• 期刊: ANIMAL CELLS AND SYSTEMS
• 影响因子: 2.9
• 作者: Park, Seahyung;Williams, Kevin W.;Sohn, Jong Woo
• 通讯作者: Sohn, Jong Woo

Glucagon-like peptide-1 (GLP-1) signalling in the brain: From neural circuits and metabolism to therapeutics.

• DOI: 10.1111/bph.15682
• 发表时间: 2022-03
• 期刊: British journal of pharmacology
• 影响因子: 7.3
• 作者: Kabahizi A;Wallace B;Lieu L;Chau D;Dong Y;Hwang ES;Williams KW
• 通讯作者: Williams KW

Exercise-induced hypothalamic neuroplasticity: Implications for energy and glucose metabolism.

• DOI: 10.1016/j.molmet.2023.101745
• 发表时间: 2023-07
• 期刊: MOLECULAR METABOLISM
• 影响因子: 8.1
• 作者: Hwang, Eunsang;Portillo, Bryan;Grose, Kyle;Fujikawa, Teppei;Williams, Kevin W.
• 通讯作者: Williams, Kevin W.