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.

我们要求资金购买家庭笼子的全面实验室动物监测系统 （蛤s-hc）来自哥伦布仪器的系统。蛤hc是一个集成系统 一次全面分析16只动物的能量平衡。该系统收集实时数据 食物摄入量，赞助活动，自愿锻炼和通过间接消耗的记录 醒着或睡觉，不受限制的动物的量热法，以提供完整的能量平衡概况 研究饮食和药物治疗在小鼠疾病模型中的影响 在退伍军人中流行，包括肥胖，糖尿病，肌肉减少症和阿尔茨海默氏病。 该系统的核心是一个温度控制的柜子，该机柜可容纳16只动物并密封 笼子。重要的是，蛤hc系统使用标准的动物外壳笼，避免了混杂的效果 关于动物行为，由于被放置在新笼子中并允许快速适应动物。 对进入笼子的新鲜空气流的精确控制，以及对小的多路复用检测 来自每个笼子内部的氧气和二氧化碳的差异可以评估 通过间接量热法的能量消耗（氧气消耗，二氧化碳产生，呼吸道 交换比率）。新一代高速二氧化二氧化锆差氧传感器与A 二氧化碳和高空流速的非分散红外传感器允许高速，准确的气体 具有高临时分辨率和灵敏度的间接热量法数据的测量。动物活动是 用一系列红外照相梁记录下来，这些光束周围围绕每个笼子并检测自发 动作作为单独的光束在x，y和z轴的每个中都断裂。可选的跑步车轮允许 评估自愿运动。最后，系统通过自动计算变化来测量食物摄入 在食品重量的内容中，费用更高。 该设备将用于通过VA优异奖资助的研究来支持几位调查员的工作 与退伍军人高有关疾病的计划。 Dudley Lamming博士研究了什么，何时以及如何 通常，我们吃的是调节健康和寿命。他将利用设备来推进他的研究 饮食的大量营养素组成，特别是饮食蛋白的精确氨基酸组成 - 调节能量平衡和血糖控制。 Rozalyn Anderson博士研究了营养敏感的 介导热量限制的代谢调节剂，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育。她将使用设备检查 脂联素信号如何改变能量消耗。 Dawn Davis博士探索了ISLEL的信号传导 调节胰腺β细胞增殖和凋亡的机制，并将探讨如何变化 胰腺模型中的胰腺内分泌功能移动了全身能量平衡。 Michelle Kimple博士 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。她会用 体内增益和功能模型的丧失，以表征这些途径在肥胖和糖尿病中的重要性。 Matthew Merrins博士研究了代谢信号如何调节胰腺β细胞的胰岛素分泌。博士 Mihaela Teodorescu研究阻塞性睡眠呼吸暂停，能量平衡和下气道的相互作用 生理。应用程序中概述了一系列正在进行的和计划的协作项目，这些项目无处不在 扩大这些计划的生产力和影响。所有这些项目对 退伍军人的健康和我们要求的蛤s-HC系统将促进这些产品的进度 以及重要的项目，并刺激与其他用户的协作工作。