Ventromedial Hypothalamic Regulation of Metabolic Changes Induced by Exercise

运动引起的代谢变化的下丘脑腹内侧调节

• 批准号: 10242071
• 负责人: JOEL K. ELMQUIST
• 金额: $ 48.56万
• 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/10242071
• 关键词: Acute; Adipose tissue; Affect; Body Composition; Body Weight decreased; Brain; Cell Nucleus; Chronic; Core Facility; Development; Eating; Energy Metabolism; Exercise; Gene Expression; Genetically Engineered Mouse; Glucose; Glutamate Transporter; Glutamates; Goals; Heart; Hepatic; High Fat Diet; Homeostasis; Hypothalamic structure; Image; Insulin Receptor; Investigation; Link; Lipids; Liver; Mediating; Metabolic; Metabolic Diseases; Metabolism; Modeling; Monitor; Mus; N-Methyl-D-Aspartate Receptors; Neuraxis; Neurons; Neurosecretory Systems; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Pancreas; Pattern; Peripheral; Pro-Opiomelanocortin; Property; Public Health; Regulation; Role; SF1; Signal Transduction; Skeletal Muscle; Synapses; Techniques; Technology; Testing; Tissues; Training; base; blood glucose regulation; endurance exercise; energy balance; exercise training; experimental study; glucose metabolism; improved; in vivo; in vivo calcium imaging; insulin sensitivity; leptin receptor; mouse model; neurotransmission; novel strategies; novel therapeutic intervention; optogenetics; predictive modeling; response; transcription factor; transmission process

ABSTRACT Exercise training markedly improves multiple metabolic parameters, including improved insulin sensitivity and body composition. Exercise also has beneficial effects on the central nervous system (CNS), which in turn, regulates all peripheral tissues, including the liver, pancreas, skeletal muscle, heart and adipose tissue. Relatively little is known about the mechanisms underlying the changes in the CNS following exercise training that contribute to the beneficial effects of exercise. Our overarching hypothesis is that exercise induces several changes in hypothalamic neurons and neuroendocrine signals, which in turn regulate food intake, body composition, exercise endurance, and insulin sensitivity in key peripheral tissues. We will systematically explore how exercise training affects in vivo activity dynamics of SF1 neurons and their targets, and determine how modulation of SF1 neurons influences insulin sensitivity and metabolic adaptations to exercise. We will also test the hypothesis that exercise training induces changes in peripheral metabolic responses that are dependent on the release of glutamate from SF1 neurons onto pro-opiomelanocortin (POMC) neurons. These studies will rely on several unique mouse models that have been developed for these studies, and cutting edge techniques including in vivo neuronal imaging and optogenetics.

摘要 运动训练显著改善多个代谢参数，包括改善胰岛素敏感性， 身体成分运动对中枢神经系统（CNS）也有有益的影响，反过来， 调节所有外周组织，包括肝脏、胰腺、骨骼肌、心脏和脂肪组织。 运动训练后中枢神经系统变化的机制目前知之甚少 有助于锻炼的有益效果。我们的总体假设是， 下丘脑神经元和神经内分泌信号的几种变化，反过来又调节食物 摄入量、身体组成、运动耐力和关键外周组织的胰岛素敏感性。我们将 系统探讨运动训练对SF1神经元及其靶点在体活动动力学的影响， 并确定SF1神经元的调节如何影响胰岛素敏感性和代谢适应， 锻炼的我们还将检验运动训练诱导外周代谢变化的假设， 依赖于SF1神经元释放谷氨酸到前阿黑皮素上的反应 （POMC）神经元。这些研究将依赖于几个独特的小鼠模型，这些模型已经开发出来， 研究和尖端技术，包括体内神经元成像和光遗传学。