Core C: Phenotyping Core

核心 C：表型核心

• 批准号: 10588797
• 负责人: Nathan R. Qi
• 金额: $ 46.52万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10588797
• 关键词: Animal Model; Animals; Anxiety; Area; Behavior; Behavioral; Biological Assay; Blood; Blood Vessels; Blood specimen; Body Fluids; Body Weight; Bolus Infusion; Cannulas; Closure by clamp; Collaborations; Conscious; Consultations; Continuous Infusion; Continuous Intravenous Infusion; Country; Culex (Genus); Data; Data Analyses; Diabesity; Diabetes Mellitus; Disease; Educational workshop; Environment; Environmental Risk Factor; Equipment; Exercise Test; Experimental Designs; Fatty Acids; Fatty acid glycerol esters; Feeding behaviors; Fiber; Fiber Optics; Functional disorder; Genetic; Germ-Free; Glucose; Glucose Clamp; Glycerol; Goals; Habits; Home; Hormone secretion; Hormones; Human Resources; Hyperinsulinism; Hypoglycemia; Indirect Calorimetry; Infusion procedures; Insulin; Isotope Labeling; Label; Laboratories; Learning; Lighting; Lipids; Lipolysis; Macronutrients Nutrition; Measurement; Measures; Memory; Metabolic; Metabolic Diseases; Metabolic dysfunction; Metabolism; Methodology; Michigan; Mission; Modeling; Molecular; Monitor; Motor Activity; Mus; Neurons; Nutrient; Obesity; Operant Conditioning; Operative Surgical Procedures; Paper; Parabiosis; Pattern; Performance; Phenotype; Photometry; Physiological; Physiology; Population; Procedures; Process; Property; Protocols documentation; Radiolabeled; Reagent; Research; Research Personnel; Resources; Role; Running; Sampling; Services; Stable Isotope Labeling; Standardization; Statistical Data Interpretation; Structure; Surgical Models; System; Taste Perception; Techniques; Technology; Testing; Time; Tissue Sample; Tissues; Tracer; Training; Triglycerides; Universities; VO2max; bariatric surgery; base; behavior test; behavioral phenotyping; blood glucose regulation; combat; cost effective; design; dietary constituent; exercise training; experience; experimental study; food consumption; glucose metabolism; in vivo; insulin sensitivity; interest; lipid metabolism; metabolic phenotype; metabolic rate; metabolomics; microbiome; mouse model; optical fiber; optogenetics; preference; respiratory; response; tool; training opportunity

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.

项目概要/摘要-核心C。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，这些服务对 肥胖、糖尿病和相关疾病的小鼠模型的体内代谢和行为表型分析。一 深入了解对营养素和环境因素的生理反应， 病理生理机制，有助于糖尿病和相关的代谢疾病是必要的，如果我们是 来有效地应对这些情况。然而，表型所需的资源和技术 探索改变葡萄糖稳态和代谢的整体动物模型， 在大多数研究人员的实验室里，根本的控制机制是不存在的。MPB核心满足 这些需求通过一个全面的，方便的，具有成本效益的平台菜单，其中包括：1） 葡萄糖稳态和代谢钳夹（核心进行高胰岛素钳夹研究，包括 小鼠中代谢物储存和释放的专门分析），2）整个动物代谢评估： CLAMS和Promethion间接量热系统用于检查代谢率、呼吸 在常规小鼠或其无菌对应物中的交换率、食物消耗和自发活动， 3)使用3 H标记的甘油三酯、脂肪酸或甘油评估组织脂质的体内脂质代谢 掺入和处置或脂解。4)代谢物的体内稳态稳定同位素标记（核心 进行大剂量连续静脉输注，以建立任何给定代谢物的稳态， 提供样本给大学的一个独立的代谢组学核心， 5）利用Culex/Empis自动化血液/体液采样和输注 远程收集系列样品并向行为自由、无压力的小鼠注入物质的平台，6） 联体共生、减肥手术或无菌小鼠的小鼠模型。这些模型由核心提供， 随后的表型分析可以用密歇根州所有核心的组合资源来进行。 MPMOD，7）运动训练和跑步能力测试，包括最大摄氧量。8)基本的行为测试， 确定一般的运动活动，焦虑，探索习惯，或空间学习的小鼠模型， 代谢功能障碍9)摄食行为：膳食微观结构和膳食强化特性 成分是衡量无论是家庭笼或操作条件反射的范例。10)活体纤维光度法 和光遗传学刺激来监测和操纵特定神经元群体中的活性，以评估它们的 在新陈代谢和行为中的作用。MPB核心还提供咨询和建议， 设计，来自一系列经验证的测定的可靠数据，与多个 研究人员和培训机会， 密歇根大学和全国各地。