Core C: Phenotyping Core

核心 C：表型核心

基本信息

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
项目类别：
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

项目摘要

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对细节至关重要的专家咨询、最先进的设备和技术服务肥胖、糖尿病和相关疾病小鼠模型的体内代谢和行为表型分析。全面了解对营养物质和环境因素的生理反应以及如果我们是这样的话，就需要了解导致糖尿病和相关代谢疾病的病理生理机制然而，要有效地对抗这些情况，需要资源和技术来表现。在揭示基本水平的水平上探索葡萄糖稳态和代谢的整个动物模型大多数研究人员的实验室不具备基本的控制机制。这些需求通过全面、便捷且具有成本效益的平台菜单实现，其中包括：1) 葡萄糖稳态和代谢钳（核心执行高胰岛素钳研究，包括对小鼠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、呼吸传统小鼠或其无菌供体的交换率、食物消耗和运动活动， 3) 使用 3H 标记的甘油三酯、脂肪酸或甘油进行体内脂质代谢以评估脂质组织掺入和处置或脂肪分解4）代谢物的体内稳态稳定同位素标记（核心）进行连续推注静脉输注以建立任何给定代谢物的稳态向大学的独立代谢组学核心提供样本，以进行代谢的进一步分析 5) 利用 Culex/Empis 自动进行血液/体液采样和输注远程收集系列样本并向行为自由、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模型这些模型由 Core 和提供。随后的表型分析可以利用密歇根州所有核心的综合资源进行 MPMOD，7) 运动训练和跑步能力测试，包括最大摄氧量 8) 基本行为测试。确定小鼠模型的一般运动活动、焦虑、探索习惯或空间学习 9) 摄入行为：膳食微观结构和膳食的强化特性。成分可通过家庭笼式或操作性调节范例进行测量 10) 体内光纤光度测定。和光遗传学刺激来监测和操纵特定神经群体的活动以评估其 MPB 核心还提供实验方面的咨询和建议。设计、来自一系列经过验证的测定的可靠数据、与多种需求相关的基本数据分析为研究人员提供核心既定方法的研究人员和培训机会密歇根大学和全国各地。