Case Mouse Metabolic Phenotyping Center

摘要 CASE-MMPC的任务是促进小鼠的表型表征 研究代谢性疾病的研究人员，重点放在糖尿病和 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。我们的利基市场是新陈代谢的测量和解释 稳定同位素示踪技术和质量辅助下的通量和代谢组型 光谱分析，重点是避免经常困扰这类方案的人工制品。这个 代谢组学和稳定同位素技术的结合使得新的 途径和新的监管机制。这种方法是在CASE-MMPC上首创的 自那以后，他获得了世界各地调查人员的青睐。我们的中心也是 协助制定NIDDK赞助的年度课程“将同位素用于 新陈代谢研究》，将于2015年11月由来自 MMPC和美国大学，并吸引了国际学生。案例-MMPC是 目前已进入运营的第9个年头。此应用程序请求支持增加 该中心的能力，扩大提供的示踪剂和测量的代谢物的资料库 包括氧化应激和炎症相关的途径。特定目标1将提供核心 为研究人员提供进行代谢通量实验的设施，利用我们在STRATE方面的专业知识 同位素示踪剂和质谱学。目标2将对小鼠组织和身体进行分析 由进行新陈代谢研究的研究人员提供的液体。这包括调查人员 在CWRU以及国内和全球的其他机构工作。在目标3中，我们将开发 其他创新示踪剂和方法用于评估氧化应激和 发炎。这涉及到一个新的“次核心”，它还将提供稳定的定制合成 脂质过氧化产物的同位素示踪和质谱分析。在《目标4》中我们将 为调查员及其工作人员提供以下方面的培训和教育：(1)熟练使用 用于代谢研究的同位素，(Ii)了解MMPC的能力并设计 对他们的问题进行适当的实验，(Iii)在他们的实验室中进行程序，以便 准备要由MMPC分析的样品，和/或(Iv)学习执行 在他们自己的实验室里完成程序。这些目标的实现可望 显著推进新陈代谢领域并协助全国克利夫兰的研究人员 在全球范围内，发现导致糖尿病和肥胖的新途径和新机制- 相关的慢性病。

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.