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.

项目摘要 /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，这对于详细信息至关重要 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。一个 了解对营养和环境因素的身体反应以及 如果我们是 有效地应对这些条件。但是，表型所需的资源和技术 探测葡萄糖稳态变化和代谢的全动物模型在一个揭示基本的水平上 大多数研究人员的实验室无法使用基本的控制机制。 MPB核心遇到 通过全面，方便且具有成本效益的平台菜单，包括：1） 葡萄糖稳态和代谢夹（核心进行高胰岛素夹具研究，包括 代谢物存储和释放的专业分析），2）全动物代谢评估： 蛤和promethion间接量热法用于检查代谢率，呼吸系统 传统小鼠或其无菌同行的交换比率，食物消耗和运动活性， 3）使用3H标记的甘油三酸酯，脂肪酸或甘油来评估组织脂质的体内脂质代谢 掺入和处置或脂解。 4）体内稳态稳定的同位素标记代谢物（核心 执行液连续静脉输注，以建立任何给定代谢物的稳态和 为大学的独立代谢组学核心提供样品，以进一步分析代谢 在组织中进行跟踪或通量），5）使用Culex/Empis进行自动血/体液采样和输注 远程收集连环样品和注入物质以自由行为的平台，无重的小鼠，6） 抛物线，减肥手术或无菌小鼠的小鼠模型。这些模型由核心提供， 随后的表型可以使用密歇根州所有核心的组合资源进行 MPMOD，7）包括VO2MAX在内的跑步能力的运动训练和测试。 8）基本的行为测试 在鼠标模型中确定一般的运动活动，动画，探索习惯或空间学习 代谢功能障碍。 9）摄入行为：饮食饮食的饮食和增强饮食特性 组成部分以家庭式或操作条件范式进行测量。 10）体内纤维光度法 和光遗传学刺激以监测和操纵特定神经元种群的活性以评估其 在代谢和行为中的作用。 MPB核心还提供有关实验的咨询和建议 设计，来自一系列经过验证测定的可靠数据，与多个需求有关的基本数据分析 研究人员和核心既定方法的培训机会既给研究人员 密歇根大学以及全国各地。