Case Mouse Metabolic Phenotyping Center

凯斯小鼠代谢表型中心

• 批准号: 9173671
• 负责人: Henri Brunengraber
• 金额: $ 30.91万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-25 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9173671
• 关键词: Body Fluids; Chronic Disease; Complement; Complex; Core Facility; Custom; Development; Diabetes Mellitus; Educational process of instructing; Elements; Faculty; Fee-for-Service Plans; Genetically Engineered Mouse; Goals; Health Benefit; Individual; Inflammation; Institution; International; Investigation; Isotopes; Kinetics; Laboratories; Learning; Lipid Peroxidation; Mass Spectrum Analysis; Measurement; Measures; Metabolic; Metabolic Diseases; Metabolism; Mission; Modus; Morphologic artifacts; Mus; National Institute of Diabetes and Digestive and Kidney Diseases; Obesity; Ohio; Oxidative Stress; Pathway interactions; Pattern; Plague; Planning Techniques; Procedures; Protocols documentation; Request for Applications; Research; Research Personnel; Sampling; Services; Techniques; Technology; Time; Tissues; Tracer; Training; Training and Education; Universities; Work; design; innovation; metabolic abnormality assessment; metabolic phenotype; metabolomics; mouse model; operation; programs; research study; stable isotope

ABSTRACT The mission of the Case-MMPC is to facilitate phenotypic characterization of mice for investigators studying metabolic diseases, with an emphasis and prioritization on diabetes and obesity. We work within the MMPC Consortium to complement and partially overlap the activities of the other six Centers. Our niche is the measurement and interpretation of metabolic fluxes and metabolomic patterns with the help of stable isotope tracer techniques and mass spectrometry, with emphasis on the avoidance of artifacts that often plague such protocols. The combination of metabolomics and stable isotope technology allows the discovery of new pathways and new regulatory mechanisms. This approach was pioneered at the Case-MMPC and has since gained favor with investigators around the world. Our Center was also instrumental in the development of the NIDDK-sponsored annual course on “Use of Isotopes for Metabolic Studies”, which will be taught for the 8th time in November 2015 by 11 faculty from MMPCs and US universities, and draws an international attendance. The Case-MMPC is currently in its 9th year of operation. This application requests support for increasing the capacity of the Center, expanding the repertoire of tracers provided and metabolites measured to include oxidative stress and inflammation-related pathways. Specific Aim 1 will provide core facilities for investigators to carry out metabolic flux experiments, utilizing our expertise in stable isotope tracers and mass spectrometry. Aim 2 will conduct analyses of murine tissues and body fluids provided by investigators carrying out metabolic studies. This includes investigators working at CWRU and in other institutions, domestic and globally. In Aim 3 we will develop additional innovative tracer and methodological approaches for assessing oxidative stress and inflammation. This involves a new “sub-core” that will also provide custom synthesis of stable isotopic tracers and mass spectrometric analysis of lipid peroxidation products. In Aim 4 we will provide training and education to investigators and their staff for, (i) proficiency in the use of isotopes for metabolic studies, (ii) understanding the capabilities of the MMPC and designing appropriate experiments for their questions, (iii) carrying out procedures in their laboratory for preparing samples to be analyzed by the MMPC, and/or (iv) learning to carrying out the complete procedure in their own laboratories. The implementation of these aims is expected to significantly advance the field of metabolism and assist investigators in Cleveland, nationally and globally, to discover new pathways and mechanisms that cause diabetes and obesity- related chronic diseases.

摘要 Case-MMPC的使命是促进小鼠的表型表征， 研究代谢疾病的研究人员，重点和优先考虑糖尿病， 肥胖我们在MMPC联盟内工作，以补充和部分重叠 其他六个中心的活动。我们的专长是测量和解释代谢 通量和代谢模式的帮助下，稳定同位素示踪技术和质量 光谱分析，重点是避免经常困扰这种协议的伪影。的 代谢组学和稳定同位素技术的结合允许发现新的 新的调控机制和机制。这种方法是在Case-MMPC中率先采用的 并获得了世界各地调查人员的青睐。我们的中心也是 在NIDDK赞助的年度课程“使用同位素 代谢研究”，这将是第8次在2015年11月由11名教师从 MMPC和美国大学，并吸引了国际出席。案件MMPC是 目前已进入运营的第九个年头。此应用程序请求支持增加 该中心的能力，扩大了所提供的示踪剂和所测量的代谢物的所有库 包括氧化应激和炎症相关途径。具体目标1将提供核心 设施的研究人员进行代谢通量实验，利用我们的专业知识，在稳定的 同位素示踪剂和质谱分析。目标2将对小鼠组织和身体进行分析 进行代谢研究的研究者提供的液体。其中包括调查人员 工作在CWRU和其他机构，国内和全球。在目标3中，我们将开发 用于评估氧化应激的其他创新示踪剂和方法学途径， 炎症这涉及到一个新的“子核心”，也将提供自定义合成稳定的 脂质过氧化产物的同位素示踪剂和质谱分析。在目标4中， 为调查人员及其工作人员提供培训和教育，以：（i）熟练使用 同位素代谢研究，（ii）了解MMPC的能力和设计 （三）在其实验室进行适当的实验， 制备待由MMPC分析的样品，和/或（iv）学习执行所述方法， 在自己的实验室完成整个过程。这些目标的实现预计将 显著推进代谢领域，并协助克利夫兰的研究人员，全国 在全球范围内，发现导致糖尿病和肥胖的新途径和机制- 相关慢性病。