Central Regulation of Sympathetic Activity to Brown Fat

交感神经活动对棕色脂肪的中枢调节

• 批准号: 7211372
• 负责人: SHAUN F MORRISON
• 金额: $ 24.5万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7211372
• 关键词: Address; Adipose tissue; Agonist; Anatomy; Animals; Appendix; Automobile Driving; Behavior; Body Weight; Brain; Brain Stem; Brain region; Brown Fat; Cell Nucleus; Cells; Cutaneous; Data; Development; Diabetes Mellitus; Dinoprostone; Disruption; Efferent Pathways; Energy Metabolism; Equation; Fever; Figs - dietary; Foundations; Funding; Genetic Models; Glucose; Glutamates; Health; Healthcare Systems; Heart Rate; Homeostasis; Human; Hypothalamic structure; Individual; Infant; Insulin; Investigation; Iontophoresis; Leptin; Lesion; Localized; Medial; Mediating; Mediator of activation protein; Metabolic; Metabolic Pathway; Metabolism; Microinjections; Modeling; Nerve; Neural Pathways; Neurons; Neurotransmitters; Numbers; Obesity; Oxygen; Pathway interactions; Peptides; Pharmacology; Physiologic Thermoregulation; Physiological; Physiology; Pontine structure; Population; Predisposition; Preoptic Areas; Principal Investigator; Procedures; Progress Reports; Quality of life; Rattus; Regulation; Reproduction; Research; Research Personnel; Role; Series; Signal Transduction; Site; Source; Special Populations Networks; Spinal; Structure of nucleus infundibularis hypothalami; Suggestion; Synapses; System; Techniques; Temperature; Testing; Text; Therapeutic; Thermogenesis; Time; Tissues; Vasoconstrictor Agents; Work; base; expectation; feeding; heart circulation; improved; in vivo; midbrain central gray substance; neural circuit; neurochemistry; neurotransmitter agonist; news; programs; research study; response

DESCRIPTION (provided by applicant): Obesity and diabetes are unusually prevalent disruptions of energy homeostatic mechanisms which have significant consequences for the health and quality of life of afflicted individuals and impose an enormous financial burden on our nation's health care system. The long-term objective of this research is to understand the central neural circuits through which the brain influences energy expenditure, a key component of energy homeostasis and body weight regulation. Treating such dysregulations of energy homeostasis would be aided by an understanding of the functional organization and neurotransmitters within the central neural pathways that are activated by metabolic signals. The proposed research plan is a logical extension of the results from the initial funding period to directly test a series of specific hypotheses represented in our model of the central neural circuits through which metabolic signals, acting within the hypothalamus, influence brown adipose tissue (BAT) thermogenesis and heart rate by changing the activity of specific populations of brainstem sympathetic premotor neurons. These studies will provide, for the first time, the unique opportunity to define each of the synaptic integration sites in the pathways by which hypothalamic neurons regulate sympathetically-mediated energy expenditure. The proposed studies to elucidate the organization, function and pharmacology of the longitudinally- organized, core pathway for the metabolically-regulated sympathetic activation of BAT thermogenesis and heart rate will combine data from anatomical tracing and immunocytochemical experiments with those from studies examining the effects on sympathetic outflows from microinjection of substances into specific brain regions to guide subsequent electrophysiological recordings from single neurons at sites in the hypothalamus, pons and medullary raphe pallidus. The three specific aims will focus on the relevant anatomical connections, the evoked physiological responses and the behavior of functionally-identified neurons in (1) the dorsomedial hypothalamus, (2) the ventromedial periaqueductal gray and (3) the medial preoptic hypothalamus, respectively, to test clearly defined hypotheses on their functional roles in the activation of RPa neurons that leads to increased energy expenditure and heart rate evoked during the response to leptin or melanocortin agonist administration. Understanding the pharmacology within this pathway driving the sympathetic responses during fever could provide a foundation for developing strategies to alter sympathetically-mediated energy expenditure in support of a reduction in energy storage depots.

描述（由申请人提供）：肥胖和糖尿病是能量稳态机制的普遍破坏，这对受苦个人的健康和生活质量产生了重大影响，并对我们国家的医疗保健系统造成了巨大的财务负担。这项研究的长期目的是了解大脑影响能量消耗的中心神经回路，这是能量稳态和体重调节的关键组成部分。通过了解由代谢信号激活的中心神经途径中的功能组织和神经递质的理解，可以帮助治疗能量稳态的这种失调。 The proposed research plan is a logical extension of the results from the initial funding period to directly test a series of specific hypotheses represented in our model of the central neural circuits through which metabolic signals, acting within the hypothalamus, influence brown adipose tissue (BAT) thermogenesis and heart rate by changing the activity of specific populations of brainstem sympathetic premotor neurons.这些研究将首次提供独特的机会，以定义下丘脑神经元调节交感神经介导的能量消耗的途径中的每个突触整合位点。提出的研究旨在阐明纵向组织的组织，功能和药理学的核心途径，用于代谢受调节的交感神经激活蝙蝠的热生成和心率的交感神经激活将结合来自解剖学追踪和免疫细胞化学实验的数据，从而从研究中效应的研究效果，从而导致型号的效果。下丘脑，PON和髓质Raphe Pallidus的神经元。这三个具体目的将集中于相关的解剖联系，诱发的生理反应以及（1）（1）在（1）背侧下丘脑下丘脑的功能识别神经元的行为导致对瘦素或黑色皮质激动剂给药的反应期间诱发的能量消耗和心率增加。了解在发烧过程中推动交感神经反应的这种途径中的药理学可以为制定改变交感神经介导的能量消耗以支持减少储能库的基础。