SHEEP Request for a Metabolic Chamber System

我们正在申请资金，为家庭笼子购买一个全面的实验室动物监测系统 哥伦布仪器公司的(CLAMS-HC)系统。CLAMS-HC是一个集成的系统，用于 一次对多达16只动物的能量平衡进行综合分析。该系统对实时数据进行采集 通过间接方式记录食物摄入量、自发活动、自愿锻炼和能量消耗 从清醒或睡眠中测量热量，不受约束的动物提供完整的能量平衡轮廓 饮食和药物治疗对高致死性疾病小鼠模型的影响 在退伍军人中很常见，包括肥胖、糖尿病、骨质疏松症和阿尔茨海默病。 这个系统的核心是一个温控柜子，里面有16只单独密封的动物 笼子。重要的是，CLAMS-HC系统使用标准的动物笼子，避免了混乱的效果 由于被放入新的笼子，并允许动物快速适应，因此对动物的行为有影响。 精确控制新风量进入笼子结合多路检测的小 来自每个笼子内部的氧气和二氧化碳的差异允许评估 间接量热法的能源消耗(氧气消耗、二氧化碳产生、呼吸 汇率)。一种新一代高速二氧化锆差动式氧传感器 二氧化碳的非色散红外传感器和高空气流量允许高速、准确的气体 间接量热数据的测量具有高时间分辨率和高灵敏度。动物的活动是 用红外线光束阵列记录，环绕每个单独的笼子并探测自发 在X、Y和Z轴的每个方向上单独折断梁时的移动。可选的走行轮允许 对自愿锻炼的评估。最后，系统通过自动计算变化来测量食物摄入量 在头顶喂食器的食物重量内容物中。 该设备将用于支持几名研究人员的工作，这些研究人员由VA Merit奖资助的研究 与退伍军人高度相关的疾病方案。达德利·拉明博士研究了什么、何时和如何 我们经常吃东西能调节健康和长寿。他将利用这些设备推进他的研究，了解 饮食的大量营养素组成--特别是饮食蛋白质的精确氨基酸组成-- 调节能量平衡和血糖控制。Rozalyn Anderson博士研究营养敏感性 调节卡路里限制益处的代谢调节剂，并将检查是否激活脂联素 用药物发出信号可以预防或治疗石棺减少症的发展。她将使用这些设备来检查 脂联素信号如何改变能量消耗。道恩·戴维斯博士探索胰岛内信号 调节胰岛β细胞增殖和凋亡的机制，并将探索 她的小鼠模型中的胰腺内分泌功能改变了全身的能量平衡。米歇尔·金普尔博士 研究G蛋白偶联受体信号转导在胰岛β细胞功能中的作用。她将在 活体功能获得和丧失模型，以表征这些途径在肥胖和糖尿病中的重要性。 马修·梅林斯博士研究代谢信号如何调节胰岛β细胞的胰岛素分泌。Dr。 米哈埃拉·特奥多雷斯库研究阻塞性睡眠呼吸暂停、能量平衡和下呼吸道的相互作用 生理学。应用程序中概述了一系列正在进行和计划中的协作项目，这将极大地 扩大这些计划的工作效率和影响。所有这些项目都对 退伍军人的健康，以及我们要求的CLAMS-HC系统将促进这些生产性的进展 和重要的项目，以及刺激与其他用户的协作努力。

We are requesting funding to purchase a Comprehensive Lab Animal Monitoring System for Home Cages (CLAMS-HC) system from Columbus Instruments. The CLAMS-HC is an integrated system for the comprehensive analysis of energy balance in up to 16 animals at one time. This system collects real-time data recordings of food intake, spontaneous activity, voluntary exercise, and energy expenditure via indirect calorimetry from awake or sleeping, unrestrained animals to provide a complete energy balance profile while studying the effects of dietary and pharmacological treatments in mouse model of diseases that are highly prevalent in Veterans, including obesity, diabetes, sarcopenia, and Alzheimer’s disease. At the core of this system is a temperature-controlled cabinet that houses 16 animals in individual and sealed cages. Importantly, the CLAMS-HC system uses standard animal housing cages, avoiding confounding effects on animal behavior as a result of being placed into new cages and permitting rapid acclimation of the animals. Precise control of the fresh air flow going into the cages combined with the multiplexed detection of small differentials of oxygen and carbon dioxide coming from the interior of each cage allows for the assessment of energy expenditure by indirect calorimetry (oxygen consumption, carbon dioxide production, respiratory exchange ratio). A new generation high speed Zirconium Dioxide differential oxygen sensor combined with a nondispersive infrared sensor for carbon dioxide and a high air flow rate permit high-speed, accurate gas measurements for indirect calorimetry data with high temporal resolution and sensitivity. Animal activity is recorded with an array of infrared photo beams that surround each individual cage and detect spontaneous movements as separate beam breaks in each of the X, Y and Z axes. Optional running wheels permit the assessment of voluntary exercise. Finally, the system measures food intake by automatically calculating changes in the food weight contents of the overhead feeder. This equipment will be used to support the work of several investigators with VA Merit Award-funded research programs on diseases of high relevance to Veterans. Dr. Dudley Lamming studies how what, when, and how often we eat regulates health and longevity. He will utilize the equipment to advance his research into how the macronutrient composition of the diet – particularly, the precise amino acid composition of the dietary protein – regulate energy balance and blood glucose control. Dr. Rozalyn Anderson investigates nutrient-sensitive metabolic regulators that mediate the benefits of caloric restriction, and will examine if activating adiponectin signaling with a drug can prevent or treat the development of sarcopenia. She will use the equipment to examine how adiponectin signaling alters energy expenditure. Dr. Dawn Davis explores the intra-islet signaling mechanisms that regulate pancreatic beta cell proliferation and apoptosis, and will explore how changes in pancreatic endocrine function in her mouse models shift whole-body energy balance. Dr. Michelle Kimple studies the role of G protein coupled receptor signal transduction in pancreatic beta cell function. She will use in vivo gain and loss of function models to characterize the importance of these pathways in obesity and diabetes. Dr. Matthew Merrins studies how metabolic signaling regulates insulin secretion by the pancreatic beta cell. Dr. Mihaela Teodorescu studies the interaction of obstructive sleep apnea, energy balance and lower airway physiology. An array of ongoing and planned collaborative projects is outlined in the application, which will vastly expand the productivity and impact of these programs. All of these projects have significant implications for Veterans' health, and the CLAMS-HC system we are requesting will facilitate the progress of these productive and important projects, as well as stimulate collaborative efforts with other users.