Metabolic Phenotyping in Live Models of Obesity and Diabetes

项目概要/摘要-总体 代谢紊乱，包括肥胖，糖尿病及其并发症是其中最紧迫的健康 世界范围内的问题，占发病率，死亡率和医疗保健成本的重大国家负担。的 密歇根大学卫生系统（现在的密歇根医学）战略性地投资于人类和 在过去20年中，我们共同努力解决这些问题。其中一个关键组成部分是 战略是促进核心实验室的发展，提供专门知识和专门服务， 整个机构的研究人员都可以获得成本。密歇根大学也是 NIDDK于2016年成立的国家联盟，用于对小鼠模型进行深入的表型检测， 肥胖症、糖尿病和相关代谢疾病，小鼠代谢表型中心（MMPC）。的 密歇根州肥胖和糖尿病活体模型的代谢表型分析（MPMOD）将建立在我们的 建立专业知识，提供标准化、高质量和最先进的体内 为全国研究人员提供表型分析服务，重点关注代表性不足的PI和小型实验室， 没有获得大量联邦研究资金的机构。密歇根州的MPMOD将是 组织在三个不同的核心：行政核心，动物护理和无菌小鼠核心， 代谢，生理和行为（MPB）表型核心。行政核心将提供 科学和财政的全面领导。它将协调各个核心之间的表型分析活动， 将促进与MPMOD联盟和协调单位的表型中心成员的互动 （CU）。动物护理和无菌小鼠核心将负责运输、住房和 动物的兽医护理将在MPB表型中心进行评估。MPB表型核心将 提供一套全面的体内评估，包括前MMPC提供的评估， 也就是说，葡萄糖或脂质稳态（葡萄糖耐量、胰岛素耐量、脂质耐量、高胰岛素血症- 具有示踪剂的正葡萄糖钳夹），整体动物能量稳态（CLAMS，SABLE， 饮食和环境温度挑战），超日激素分泌（库蚊平台系列 从没有人类存在的自由移动小鼠中采集生物流体样品），行为测量（例如， 享乐和稳态进食反应，以及肥胖和/或糖尿病相关的学习变化， 焦虑和抑郁）等。使用高度专业化的外科手术的附加体内服务（例如， 慢性门静脉插管、联体共生和立体定位脑手术）、光遗传学和纤维光度测定 技术.总之，密歇根MPMOD将提供广泛的先进体内 表型分析服务、咨询和培训，利用我们完善的代谢表型分析 设施和独特的专业知识下丘脑功能，小鼠遗传学和专业手术， 实验动物

Project Summary / Abstract – Overall Metabolic disorders, including obesity, diabetes and their complications are among the most pressing health issues worldwide accounting for a substantial national burden of morbidity, mortality, and healthcare costs. The University of Michigan Health System (now Michigan Medicine) has strategically invested in both human and physical resources over the past 20 years in a concerted attack on these problems. A key component of this strategy is to foster the development of core laboratories providing expertise and specialized services at accessible cost to researchers throughout the institution. The University of Michigan is also a member of the national consortium established in 2016 by the NIDDK for in-depth phenotyping tests of mouse models of obesity, diabetes, and related metabolic conditions, the Mouse Metabolic Phenotyping Centers (MMPC). The Michigan Metabolic Phenotyping in Live Models of Obesity and Diabetes (MPMOD) will build upon our stablished expertise to provide a unique pallet of standardized, high quality and state-of-the-art in vivo phenotyping services for researchers nationwide with focus on underrepresented PIs and small laboratories or institutions that have not received significant federal research funding. The MPMOD at Michigan will be organized in three distinct cores: The Administrative Core, the Animal Care and Germ-Free Mouse Core, and the Metabolic, Physiological and Behavioral (MPB) Phenotyping Core. The Administrative Core will provide overall scientific and fiscal leadership. It will coordinate phenotyping activities among the individual cores and will foster interaction with phenotyping centers members of the MPMOD Consortium and the Coordinating Unit (CU). The Animal Care and Germ-Free Mouse Core will be responsible for transportation, housing, and veterinary care of animals to be assessed at the MPB Phenotyping Core. The MPB Phenotyping Core will provide a comprehensive battery of in vivo assessments encompassing those provided by the former MMPC, i.e., glucose or lipid homeostasis (glucose tolerance, insulin tolerance, lipid tolerance, hyperinsulinemic- euglycemic clamps with tracers), whole-animal energy homeostasis (indirect calorimetry by CLAMS, SABLE, with dietary and environmental temperature challenges), ultradian hormone secretion (Culex platform for serial biological fluid sampling from free-moving mice without human presence), behavioral measurements (e.g., hedonic and homeostatic feeding responses, and obesity- and/or diabetes-associated changes in learning, anxiety and depression), etc. Additional in vivo services using highly specialized surgical procedures (e.g., chronic portal vein cannulation, parabiosis, and stereotaxic brain surgeries), optogenetic and fiber photometry technologies. Together, the Michigan MPMOD will provide access to a broad range of advanced in vivo phenotyping services, consultation and training taking advantage of our well-stablished metabolic phenotyping facilities and unique expertise on hypothalamic function, mouse genetics and specialized surgeries in experimental animals.