Core C: Phenotyping Core

项目摘要/摘要-核心C.新陈代谢、生理和行为表型核心 代谢、生理和行为(MPB)表型核心的目的和主要目标是 提供专家咨询、最先进的设备和技术服务，这些对于 肥胖、糖尿病和相关疾病小鼠模型的体内代谢和行为表型。一个 深入了解营养物质和环境因素的生理反应，以及 如果我们需要糖尿病和相关代谢性疾病的病理生理机制 以有效地抗击这些状况。然而，表型所需的资源和技术 探索葡萄糖动态平衡和代谢改变的整个动物模型，其水平揭示了 大多数研究人员的实验室都没有潜在的控制机制。MPB核心会议 通过全面、方便且经济实惠的平台菜单满足这些需求，其中包括：1) 葡萄糖动态平衡和代谢钳(核心执行高胰岛素钳研究，包括 小鼠体内代谢物储存和释放的专门分析)，2)整个动物代谢评估： 文蛤和扑尔敏间接量热法系统用于检测代谢率、呼吸 常规小鼠或其无菌小鼠的交换率、食物消耗和运动活动， 3)用~3H标记的甘油三酯、脂肪酸或甘油在体内的脂肪代谢来评估组织的脂质 合并和处置或脂肪分解。4)代谢产物(核心)的体内稳态稳定同位素标记 进行团注-持续静脉输液，以建立任何给定代谢物的稳定状态 为大学的一个独立代谢组学中心提供样本，用于进一步的代谢分析 组织中的示踪或流量)，5)利用库雷克斯/Empis的自动血液/体液采样和输注 远程采集系列样本并向行为自由、不受压力的小鼠注入物质的平台，6) 异型繁殖的小鼠模型、减肥手术或无菌小鼠。这些型号由Core和 可以利用密歇根地区所有岩心的组合资源进行后续表型鉴定 MPMOD，7)运动训练和跑步能力测试，包括最大摄氧量。8)基本行为测试 测定小鼠模型的一般运动活动、焦虑、探索习惯或空间学习 代谢功能障碍。9)进食行为：膳食微结构与日粮补益特性 成分是在家庭笼子或操作条件作用范式中测量的。10)活体纤维光度法 和光遗传刺激，以监测和操纵特定神经元群体的活动，以评估他们的 在新陈代谢和行为中的作用。MPB核心还提供关于实验的咨询和建议 设计、来自一系列经过验证的分析的可靠数据、与多项需求相关的基本数据分析 向研究人员提供建立核心方法学方面的研究人员和培训机会 密歇根大学和全国各地。

Project Summary / Abstract – Core C. Metabolic, Physiological and Behavioral Phenotyping Core The purpose and primary goals of the Metabolic, Physiological and Behavioral (MPB) Phenotyping Core are to provide expert consultation, state-of-the art equipment, and technical services that are critical for the detailed in vivo metabolic and behavioral phenotyping of mouse models of obesity, diabetes, and associated disorders. A thorough understanding of the physiological responses to nutrients and environmental factors and of the pathophysiological mechanisms that contribute to diabetes and related metabolic diseases is required if we are to effectively combat these conditions. However, the resources and technology necessary to phenotypically probe whole animal models of altered glucose homeostasis and metabolism at a level that reveals basic underlying mechanisms of control are not available in most investigators’ laboratories. The MPB Core meets these needs through a comprehensive, convenient, and cost-effective menu of platforms that includes: 1) Glucose homeostasis and metabolic clamps (the Core performs hyperinsulinemic clamp studies including specialized analysis of metabolite storage and release in mice), 2) Whole animal metabolic assessment: The CLAMS and Promethion indirect calorimetry systems are used to examine metabolic rate, respiratory exchange ratio, food consumption, and locomotor activity in conventional mice or their germ-free counterparts, 3) In vivo lipid metabolism using 3H-labeled triglyceride, fatty acid, or glycerol for assessment of the tissue lipid incorporation and disposal or lipolysis. 4) In vivo steady-state stable isotope labeling of metabolites (the core performs bolus-continuous intravenous infusion to establish a steady-state of any given metabolite and provides samples to an independent Metabolomics Core at the university for further analyses of metabolic tracing or fluxes in tissues), 5) Automated blood/body fluids sampling and infusion utilizing a Culex/Empis platform to remotely collect serial samples and infuse substances to freely behaving, unstressed mice, 6) Mouse models of parabiosis, bariatric surgery, or germ-free mice. These models are provided by the Core and subsequent phenotyping can be performed with the combined resources of all the Cores in the Michigan MPMOD, 7) Exercise training and testing of running capacity including VO2max. 8) Basic behavioral tests to determine general locomotor activity, anxiety, exploration habits, or spatial learning in mouse models of metabolic dysfunction. 9) Ingestive behavior: Meal microstructure and reinforcing properties of dietary constituents are measured in either home-cage or operant-conditioning paradigms. 10) in vivo fiber photometry and optogenetic stimulation to monitor and manipulate activity in specific neuronal populations to assess their role in metabolism and behavior. The MPB Core also provides consultation and advice on experimental design, reliable data from a range of validated assays, essential data analysis relevant to the needs of multiple investigators and training opportunities in the established methodologies of the Core to researchers both at the University of Michigan and throughout the country.