Thermoregulatory circuits that regulate feeding

项目摘要 温度调节和能量平衡系统紧密耦合，以确保两个核心的稳定性 温度和体脂在广泛的环境温度范围内储存。这种互动是 突出表现为对寒冷暴露的适应性代谢反应，因为增加产热量需要 保持核心体温的同时，要按比例增加能量摄入量，以维持身体脂肪 压力。这些适应性反应是快速和强大的，我们最近的发现暗示了刺鼠的作用- 相关肽(AgRP)神经元在适应性摄食反应中的作用 暴露，这种激活是冷诱导的吞噬作用所必需的，但不是冷诱导的生热所必需的 回应。该提案的首要目标是确定将体温调节与 控制AgRP神经元的活动和相关的摄食反应。拟议的研究寻求1)检查 环境温度、AgRP神经元活性变化与相关摄食的时间关系 反应和2)识别和表征将体温调节与冷诱导联系起来的神经回路 吞噬过多。为了实现这一目标，包括化学遗传学在内的最先进的神经科学技术， 利用光遗传学和纤维光度系统的方法，结合免疫组织化学。 和高级代谢表型。总之，这项工作将促进对神经回路的理解 将体温调节与AgRP神经元和摄食联系起来，并可能确定治疗糖尿病的新策略 通过钝化相关的过度吞噬反应而导致肥胖。

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.