Thermoregulatory circuits that regulate feeding

调节喂养的温度调节电路

• 批准号: 10400898
• 负责人: GREGORY J MORTON
• 金额: $ 52.56万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10400898
• 关键词: Acute; Biological Models; Body Temperature; Body Weight decreased; Body fat; Brain; Closure by clamp; Coupled; Cues; Cutaneous; Data; Dose; Eating; Energy Intake; Energy Metabolism; Ensure; Environment; Exposure to; Fiber; Future; Goals; Homeostasis; Hyperphagia; Hypothalamic structure; Leptin; Link; Medial Dorsal Nucleus; Mediating; Medical Care Costs; Metabolic; Modeling; Modernization; Mus; Nature; Neurons; Neurosciences; Obesity; Peptides; Perception; Photometry; Physiologic Thermoregulation; Plasma; Play; Population; Preoptic Areas; Regulation; Reporting; Role; Secondary to; Skin; Societies; Stress; Structure of nucleus infundibularis hypothalami; System; Techniques; Temperature; Temperature Sense; Thermogenesis; Tyrosine 3-Monooxygenase; Work; base; designer receptors exclusively activated by designer drugs; energy balance; excessive weight gain; falls; feeding; in vivo; metabolic phenotype; neural circuit; novel; novel strategies; obesity treatment; optogenetics; paraventricular nucleus; pituitary adenylate cyclase activating polypeptide; prevent; recruit; reduced food intake; response; temporal measurement

Project Summary The thermoregulatory and energy homeostasis systems are tightly coupled to ensure the stability of both core temperature and body fat stores across a wide range of environmental temperatures. This interaction is highlighted by the adaptive metabolic response to cold exposure, as the increase of heat production needed to maintain core temperature is accompanied by a proportionate increase in energy intake to maintain body fat stress. These adaptive responses are rapid and robust and our recent findings implicate a role for agouti- related peptide (Agrp) neurons in the adaptive feeding response since Agrp neurons are activated during cold- exposure, and this activation is required for cold-induced hyperphagia, but not cold-induced thermogenic responses. The overarching goal of the proposal is to identify the neurocircuitry linking thermoregulation to control of Agrp neuronal activity and associated feeding responses. Proposed studies seek 1) to examine the temporal relationship between changes in ambient temperature, Agrp neuron activity and associated feeding responses and 2) to identify and characterize neurocircuits that link thermoregulation to cold-induced hyperphagia. To accomplish this, state-of-the-art neuroscience techniques including chemogenetics, optogenetics and fiber photometry systems approaches are utilized, in combination with immunohistochemical and advanced metabolic phenotyping. Together, this work will advance the understanding of the neurocircuitry linking thermoregulation to Agrp neurons and feeding and may identify novel strategies for the treatment of obesity by blunting the associated hyperphagic response.

项目概要 体温调节和能量稳态系统紧密耦合，确保两个核心的稳定性 温度和身体脂肪在各种环境温度下储存。这个交互是 强调了对寒冷暴露的适应性代谢反应，因为产生的热量需要增加 维持核心温度的同时会相应增加能量摄入以维持体脂 压力。这些适应性反应是快速而有力的，我们最近的发现暗示了刺豚鼠的作用 相关肽（Agrp）神经元在适应性进食反应中的作用，因为 Agrp 神经元在寒冷期间被激活 暴露，并且这种激活是冷诱导的食欲亢进所必需的，但冷诱导的产热则不需要 回应。该提案的总体目标是确定将温度调节与 控制 Agrp 神经元活动和相关的进食反应。拟议的研究旨在 1) 检验 环境温度变化、Agrp 神经元活动和相关进食之间的时间关系 反应，2) 识别和表征将温度调节与冷诱导联系起来的神经回路 食欲亢进。为了实现这一目标，需要最先进的神经科学技术，包括化学遗传学、 利用光遗传学和光纤光度测量系统方法，并结合免疫组织化学 和先进的代谢表型。总之，这项工作将增进对神经回路的理解 将温度调节与 Agrp 神经元和喂养联系起来，可能会确定治疗 通过减弱相关的食欲亢进反应来预防肥胖。