SHEEP Request for a Metabolic Chamber System

SHEEP 请求代谢室系统

• 批准号: 10176787
• 负责人: Dudley William Lamming
• 金额: --
• 依托单位: WM S. MIDDLETON MEMORIAL VETERANS HOSP
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2021-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10176787
• 关键词: Acclimatization; Age; Aging; Air; Air Movements; Alzheimer' s Disease; Amino Acids; Animal Behavior; Animal Housing; Animals; Apoptosis; Award; Basic Science; Blood Circulation; Blood Glucose; Caloric Restriction; Carbohydrates; Carbon Dioxide; Cardiovascular Diseases; Cell Proliferation; Cell physiology; Computer software; Computers; Custom; Data; Data Analyses; Data Collection; Detection; Development; Diabetes Mellitus; Diet; Dietary Proteins; Disease; Disease model; Eating; Energy Metabolism; Environment; Equation; Equipment; Exercise; Extravasation; Fatty acid glycerol esters; Food; Funding; G Protein-Coupled Receptor Signaling; Gases; Generations; Health; High Prevalence; Home; Hospitals; Indirect Calorimetry; Individual; Islets of Langerhans; Lighting; Longevity; Longitudinal Studies; Macronutrients Nutrition; Measurement; Measures; Mediating; Metabolic; Metabolism; Modeling; Monitor; Movement; Mus; Nutrient; Obesity; Obstructive Sleep Apnea; Output; Oxygen; Oxygen Consumption; Pathway interactions; Pharmaceutical Preparations; Pharmacological Treatment; Physiology; Prevalence; Process; Production; Productivity; Proteins; Records; Reproducibility; Research; Research Personnel; Rodent; Rodent Model; Role; Running; Sampling; Scanning; Signal Transduction; Site; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Speed; Stress; Structure of beta Cell of islet; System; Temperature; Thermogenesis; Time; Training; Translational Research; Veterans; Weight; Work; adiponectin; awake; blood glucose regulation; design; dietary; energy balance; feeding; improved; in vivo; instrument; instrumentation; insulin secretion; islet; loss of function; metabolic abnormality assessment; monitoring device; mouse model; multiplex detection; next generation; prevent; programs; respiratory; sarcopenia; seal; sensor; sensor technology; temporal measurement; translational research program; zirconium oxide

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.

我们正在请求资金购买用于家庭笼子的综合实验动物监测系统 (CLAMS-HC) 系统来自 Columbus Instruments CLAMS-HC 是一个集成系统。 该系统可同时收集多达 16 只动物的能量平衡综合分析。 通过间接记录食物摄入量、自发活动、自愿锻炼和能量消耗 对清醒或睡眠、不受约束的动物进行热量测量，以提供完整的能量平衡曲线，同时 研究饮食和药物治疗对患有高度严重疾病的小鼠模型的影响 退伍军人中普遍存在这种疾病，包括肥胖、糖尿病、肌肉减少症和阿尔茨海默病。 该系统的核心是一个温控柜，里面单独密封地饲养着 16 只动物。 重要的是，CLAMS-HC 系统使用标准动物饲养笼，避免了混淆效应。 由于被放入新笼子并允许动物快速适应而对动物行为产生影响。 精确控制进入笼内的新鲜空气流量并结合微小颗粒物的多重检测 来自每个笼子内部的氧气和二氧化碳的差异允许评估 通过间接量热法测定能量消耗（耗氧量、二氧化碳产生量、呼吸量） 新一代高速二氧化锆差动氧传感器与 用于二氧化碳的非色散红外传感器和高空气流速可实现高速、准确的气体分析 具有高时间分辨率和灵敏度的间接量热数据测量。 用围绕每个笼子的一系列红外光束进行记录并检测自发的 可选的走轮允许在 X、Y 和 Z 轴上进行单独的光束断裂运动。 最后，系统通过自动计算变化来测量食物摄入量。 在高架喂食器的食物重量含量中。 该设备将用于支持几位研究人员进行 VA 优异奖资助的研究工作 达德利·拉明博士研究了与退伍军人高度相关的疾病的内容、时间和方式。 我们经常吃的食物可以调节健康和寿命。他将利用这些设备来推进他的研究。 饮食的宏量营养素成分 - 特别是膳食蛋白质的精确氨基酸成分 - 调节能量平衡和血糖控制 Rozalyn Anderson 博士研究营养敏感性。 介导热量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肌肉减少症的发展。她将使用该设备进行检查。 Dawn Davis 博士探索脂联素信号传导如何改变能量消耗。 调节胰腺β细胞增殖和凋亡的机制，并将探讨如何变化 米歇尔·金普尔博士的小鼠模型中的胰腺内分泌功能改变了全身能量平衡。 她将研究 G 蛋白偶联受体信号转导在胰腺 β 细胞功能中的作用。 体内功能获得和丧失模型来表征这些途径在肥胖和糖尿病中的重要性。 Matthew Merrins 博士研究代谢信号如何调节胰腺 β 细胞的胰岛素分泌。 Mihaela Teodorescu 研究阻塞性睡眠呼吸暂停、能量平衡和下呼吸道之间的相互作用 申请中概述了一系列正在进行的和计划中的合作项目，这些项目将极大地发挥作用。 扩大这些计划的生产力和影响力所有这些项目都具有重大影响。 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工作的进展 和重要项目，以及激发与其他用户的协作努力。