Thermoregulatory circuits that regulate feeding

项目摘要 体温调节和能量稳态系统紧密耦合，以确保两个核心的稳定性。 温度和身体脂肪储存在广泛的环境温度范围内。这种相互作用 强调了适应性代谢反应冷暴露，因为需要增加热量生产， 维持核心温度伴随着能量摄入的成比例增加，以维持身体脂肪 应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agglutinin的作用， 相关肽（Agrp）神经元在适应性摄食反应中的作用，因为Agrp神经元在冷- 暴露，这种激活是冷诱导的摄食过多所必需的，但不是冷诱导的产热 应答该提案的首要目标是确定神经回路连接温度调节， 控制Agrp神经元活动和相关的进食反应。拟议的研究寻求1）审查 环境温度变化、Agrp神经元活动和相关摄食之间的时间关系 反应和2）识别和表征神经回路，将温度调节与冷诱导 食欲过盛为了实现这一点，最先进的神经科学技术，包括化学遗传学， 光遗传学和纤维光度测定系统方法与免疫组织化学结合使用。 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神经元和进食联系起来，并可能确定治疗 通过减弱相关的摄食过多反应来治疗肥胖。

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.