Metabolic Phenotyping in Live Models of Obesity and Diabetes

肥胖和糖尿病活体模型的代谢表型分析

• 批准号: 10588794
• 负责人: Carol Fuzeti Elias
• 金额: $ 74.1万
• 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/10588794
• 关键词: Accounting; Advertising; Animal Experiments; Animal Model; Animals; Anxiety; Area; Basic Science; Behavior assessment; Behavioral; Biological; Biomedical Research; Blood specimen; Cannulations; Chronic; Circadian Dysregulation; Consultations; Core Facility; Culex (Genus); Data; Databases; Development; Diabetes Mellitus; Educational workshop; Experimental Designs; Fiber; Fostering; Funding; Genetic; Germ-Free; Glucose; Glucose Clamp; Goals; Grant; Health; Health Care Costs; Health system; Homeostasis; Hormone secretion; Hormones; Housing; Human; Hyperinsulinism; Hypothalamic structure; Indirect Calorimetry; Individual; Indwelling Catheter; Institution; Investments; Laboratories; Leadership; Learning; Lipids; Liquid substance; Medicine; Mental Depression; Metabolic; Metabolic Diseases; Metabolism; Michigan; Modeling; Morbidity - disease rate; Motor Activity; Mus; National Institute of Diabetes and Digestive and Kidney Diseases; Obesity; Operant Conditioning; Operative Surgical Procedures; Parabiosis; Pathogenesis; Pattern; Phenotype; Photometry; Physical activity; Physiological; Physiology; Portal vein structure; Protocols documentation; Reproducibility; Research; Research Personnel; Resources; Role; Sampling; Services; Standardization; Technology; Temperature; Testing; Tracer; Training; Training Programs; Translational Research; Transportation; Universities; animal care; arm; base; behavior measurement; behavioral phenotyping; behavioral response; blood glucose regulation; brain surgery; burden of illness; comorbidity; cost; dietary; experience; feeding; glucose tolerance; hedonic; improved; in vivo; insulin tolerance; member; metabolic phenotype; mortality; mouse genetics; mouse model; novel; novel therapeutic intervention; obesity treatment; optogenetics; outreach; response; tool

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.

项目总结/摘要——总体 代谢紊乱，包括肥胖、糖尿病及其并发症是最紧迫的健康问题 世界范围内的问题给国家带来了巨大的发病率、死亡率和医疗费用负担。 密歇根大学医疗系统（现为密歇根医学）对人类和 过去 20 年来对物理资源的协调一致是解决这些问题的一个关键组成部分。 战略是促进核心实验室的发展，提供专业知识和专门服务 密歇根大学也是该机构的成员。 NIDDK 于 2016 年成立的国家联盟，旨在对小鼠模型进行深入的表型测试 肥胖、糖尿病和相关代谢状况，小鼠代谢表型中心 (MMPC)。 肥胖和糖尿病活体模型中的密歇根代谢表型分析 (MPMOD) 将建立在我们的基础上 成熟的专业知识可提供标准化、高质量和最先进的体内独特托盘 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 和小型实验室或 密歇根州 MPMOD 尚未获得大量联邦研究资助的机构将被取消。 由三个不同的核心组成：行政核心、动物护理和无菌小鼠核心，以及 代谢、生理和行为 (MPB) 表型核心将提供管理核心。 它将协调各个核心和财务部门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交通、住房和服务。 MPB 表型核心将评估动物的兽医护理。 提供全面的体内评估，包括前 MMPC 提供的评估， 即葡萄糖或脂质稳态（葡萄糖耐量、胰岛素耐量、脂质耐量、高胰岛素血症） 带有示踪剂的血糖正常钳），整个动物能量稳态（通过 CLAMS、SABLE 进行间接量热法， 饮食和环境温度的挑战），超电激素分泌（Culex 平台系列 从没有人类存在的自由活动的小鼠身上采集生物液体样本），行为测量（例如， 享乐和稳态喂养反应，以及肥胖和/或糖尿病相关的学习变化， 使用高度专业化的外科手术（例如， 慢性门静脉插管、联体共生和脑立体定位手术）、光遗传学和光纤光度测定 密歇根 MPMOD 将共同提供各种先进的体内技术。 利用我们成熟的代谢表型分析提供表型分析服务、咨询和培训 下丘脑功能、小鼠遗传学和专门手术方面的设施和独特的专业知识 实验动物。