Neural circuitry responsible for metabolic inhibition of adaptive thermogenesis

负责适应性生热代谢抑制的神经回路

• 批准号: 7837513
• 负责人: CHRISTOPHER J MADDEN
• 金额: $ 32.06万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7837513
• 关键词: Acute; Adipocytes; Adrenergic Receptor; Adult; Area; Biological Models; Body Weight; Body Weight decreased; Brown Fat; Caloric Restriction; Cells; Clinical; Data; Development; Diabetes Mellitus; Disease; Energy Intake; Energy Metabolism; Epidemic; Excision; Face; Fasting; Foundations; Homeostasis; Human; Hypothalamic structure; Incidence; Knowledge; Malignant Neoplasms; Mediating; Metabolic; Metabolism; Modeling; Morbidity - disease rate; Nerve; Neural Pathways; Neuraxis; Neurons; Neuropeptide Y Receptor; Neurotransmitters; Obesity; Overweight; Pathway interactions; Pharmacology; Regulation; Research; Risk; Role; Series; Techniques; Testing; Thermogenesis; Tissues; United States; Weight Gain; Work; combat; diabetes risk; dietary restriction; hypertensive heart disease; in vivo; mortality; neural circuit; neuropeptide Y; novel; paraventricular nucleus; presynaptic; receptor; therapeutic development; therapeutic target

Project Summary The long term objective of this research is to gain an understanding of the neural pathways and cellular mechanisms that are involved in the metabolic regulation of energy expenditure thereby providing therapeutic targets for increasing energy expenditure and combating obesity. The proposed research plan is a comprehensive, logically-organized, hypothesis-driven series of studies to examine a novel mechanism for a fundamental regulation of energy expenditure (decreased sympathetic activation of brown adipose tissue in situations of decreased fuel availability) that may contribute to the inability to lose body weight by caloric restriction. This model is especially relevant since new data demonstrate brown adipose tissue in adult humans and both clinical and non-human studies demonstrate that the functional amount of this tissue is inversely correlated with obesity. The proposed studies will utilize functional neuroanatomical and in vivo electrophysiological techniques to elucidate the organization and pharmacology of the neural pathway responsible for the glucoprivation or fasting-induced decrease in sympathetic activation of brown adipose tissue. The three specific aims will test clearly defined hypotheses on the functional roles of specific neurochemically-defined neurons in the ventrolateral medulla, the paraventricular nucleus of the hypothalamus, and the raphe pallidus area in the glucoprivation-induced decrease in energy expenditure in brown adipose tissue. Understanding the neural pathways and mechanisms that inhibit sympathetic outflow to brown adipose tissue will provide a foundation for determining how alterations in these pathways contribute to overweight and obesity, and will represent an important step towards the development of therapeutic approaches to increase energy expenditure even in the face of dietary restriction and thereby combat obesity.

项目概要 这项研究的长期目标是了解神经网络 参与代谢调节的途径和细胞机制 能量消耗从而提供增加能量的治疗目标 支出和对抗肥胖。拟议的研究计划是一项全面的、 逻辑组织、假设驱动的一系列研究，以检验一种新的机制 用于能量消耗的基本调节（减少交感神经的激活） 棕色脂肪组织（在燃料可用性降低的情况下）可能有助于 无法通过热量限制来减轻体重。这个模型特别相关 因为新数据表明成年人体内存在棕色脂肪组织，无论是临床还是 非人类研究表明，该组织的功能量成反比 与肥胖有关。 拟议的研究将利用功能神经解剖学和体内 电生理学技术阐明细胞的组织和药理学 负责葡萄糖缺乏或禁食引起的减少的神经通路 棕色脂肪组织的交感神经激活。三个具体目标将考验明确 关于特定神经化学定义的神经元功能作用的明确假设 位于延髓腹外侧、下丘脑室旁核和 中缝苍白区在葡萄糖缺乏引起的能量消耗减少中 棕色脂肪组织。了解抑制的神经通路和机制 棕色脂肪组织的交感神经流出将为确定提供基础 这些途径的改变如何导致超重和肥胖，并将 代表着朝着开发治疗方法迈出的重要一步 即使面临饮食限制，也会增加能量消耗，从而对抗 肥胖。