The National Center for Metabolic Phenotyping of Mouse Models of Obesity and Diabetes (MPMOD) at UC Davis

加州大学戴维斯分校国家肥胖和糖尿病小鼠模型代谢表型中心 (MPMOD)

• 批准号: 10588971
• 负责人: KC KENT LLOYD
• 金额: $ 75.88万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 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/10588971
• 关键词: Acceleration; Adult; Age Years; Animals; Anxiety; Attention; Autopsy; Awareness; Behavior; Bioenergetics; Biomedical Research; Body Composition; Businesses; California; Cardiovascular system; Caring; Centers for Disease Control and Prevention (U.S.); Chronic stress; Client; Communities; Complex; Consultations; Continuous Glucose Monitor; Data; Data Analyses; Development; Diabetes Mellitus; Diabetic mouse; Diagnostic; Disease; Disease model; Eating; Energy Intake; Energy Metabolism; Environmental Risk Factor; Epidemic; Evaluation; Exercise; Experimental Designs; Feasibility Studies; Fee-for-Service Plans; Feeding behaviors; Fees; Food; Foundations; Functional disorder; Funding; Genetic; Gnotobiotic; Goals; Health; Heart Diseases; Heterogeneity; Hispanic-serving Institution; Histopathology; Human; Image; Impaired cognition; In Vitro; Incidence; Income; Infrastructure; Institution; International; Investments; Kidney; Learning; Macronutrients Nutrition; Malignant Neoplasms; Measures; Memory; Mental Depression; Metabolic; Metabolic Diseases; Metabolism; Microsurgery; Modeling; Morbidity - disease rate; Motor; Mus; Mutant Strains Mice; National Institute of Diabetes and Digestive and Kidney Diseases; Neurologic; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Operative Surgical Procedures; Organ; Outcome Measure; Participant; Pathogenesis; Persons; Phenotype; Physical activity; Physiologic Thermoregulation; Physiological; Physiology; Pilot Projects; Plasma; Population; Positron-Emission Tomography; Prediabetes syndrome; Prevalence; Prevention; Prevention strategy; Procedures; Production; Reporting; Research; Research Personnel; Resources; Role; Scientist; Serum; Services; Sleep; Solid; Specialist; Stress; Stroke; Surgical Models; System; Technology; Testing; Therapeutic; Tissues; Training and Education; Translating; Translational Research; Underrepresented Populations; Universities; Writing; adult obesity; aged; bariatric surgery; behavior test; behavioral phenotyping; clinically relevant; cost; diabetic; disease diagnosis; economic cost; energy balance; experience; experimental study; gastrointestinal; high risk; imaging capabilities; improved; in vivo; innovation; member; metabolic phenotype; microbiome; mouse model; neurobehavioral; neurophysiology; novel; patient population; programs; repository; respiratory; response; sobriety; statistics; success; training opportunity; waiver

National Center for Metabolic Phenotyping in Live Models of Obesity and Diabetes (MPMOD) at UC Davis ABSTRACT—OVERALL SECTION According to the Centers for Disease Control, more than a third of U.S. adults are obese, suffer related complications (e.g., heart disease, stroke, cancer), and cost the US economy more than $150 billion annually. And the facts don’t stop there: recent data from the CDC reveal an increasing incidence of type 2 diabetes, reaching a prevalence of ~11% of the US adult population today. Genetics, environmental factors, food and physical activity behaviors, chronic stress, and coincident high-risk morbidities all point to diabetes and obesity being diseases of heterogenic origin. In this context, advanced research to comprehensively phenotype better mouse models relevant to the human condition is especially needed to fully understand disease pathogenesis and mechanisms to inform strategies for curbing this rising epidemic. Translational research in vivo using genetic, surgical, humanized, and other types of mouse models are needed especially now to characterize disease pathogenesis, mechanisms, and consequences. These models need to be relevant to the pathophysiology of human metabolic disease so as to inform more effective diagnostic, therapeutic, and prevention strategies. To catalyze this effort and accelerate progress toward these goals, UC Davis proposes the creation of a National Center for Metabolic Phenotyping of Mouse Models of Obesity and Diabetes (MPMOD). The Center will provide the diabetes and obesity research communities access to specialized and advanced resources to assess mouse models employing unique, complex, and hard-to-find tests and procedures. MPMOD users will also be connected to competent, experienced, and expert consultation and advice on experimental design, test selection, outcomes measures, and interpretation. The UC Davis MPMOD team has a solid foundation of service to the research community: for the last 10 years, UC Davis served as a flagship in the NIDDK Metabolic Mouse Phenotyping Center (MMPC) Consortium, providing in vivo services on live mice and in vitro analyses on murine tissue and plasma and serum to the greater research community. The MPMOD Center at UC Davis will build from those successes and our strong infrastructure to offer many novel and innovative approaches to tackle new questions in live mice, drawing upon the larger UC Davis scientific enterprise and core labs to provide the research community with high quality metabolic, physiologic, and behavioral phenotyping services in vivo to characterize the heterogeneity, pathogenesis, and consequences of diabetes, obesity, and related metabolic disorders. The MPMOD Center at UC Davis will consist of an Administrative Core providing administrative, service, and business oversight for the Center; an Animal Core that will import and provide husbandry, care, and numerous special services (e.g., SPF husbandry, gnotobiotic mouse management, ABSL3 conditions, microsurgery capability, necropsy and histopathology) for mice submitted to the Center; a Metabolism and Metabolic Health Core with significant resources and expertise to offer well-established metabolic phenotyping tests plus innovative approaches (e.g., PET imaging, continuous glucose monitoring, sophisticated energy balance measures, xenometabolomics) to reveal subtle shifts in macronutrient metabolism, energy intake and feeding behaviors, energy expenditure and metabolic efficiency; and a Physiology and Behavior Core with substantial breadth and depth of expertise and capabilities to provide in-depth assessments of organ and whole-animal physiology (cardiovascular, gastrointestinal, renal, respiratory, ocular, and neurological) and neurobehavioral assessment of exercise behavior, sleep, learning and memory, anxiety, depression and stress, and motor function relevant to diabetes and obesity. Each of the Cores will have a Scientific Leader and co-Leader, Core Coordinator, and Technical Specialists to conduct experiments. Numerous Scientific Consultants affiliated with each Core will be available to offer expert advice on experimental design, test selection, and data interpretation, and provide novel and complex tests and procedures upon request. In addition to comprehensive tests and consultation, a major strength of the MPMOD Center at UC Davis will be a close association with internationally recognized assets for production and sharing of novel mouse disease models. Scientists can of course send in their own mice for testing, but in addition they can order a mouse model of diabetes or obesity from a repository (e.g., the UC Davis MMRRC, KOMP2 programs) or have the Center make a relevant mouse model de novo (e.g., genetically-altered, bariatric surgery model) for them. Services will be offered at reasonable cost to all users who will be afforded equal service priority whether from inside UC Davis or an outside institution. The Center will reinvest program income to develop new testing technologies, fund collaborative projects, support fee waivers, and subsidize pilot and feasibility studies. The Center intends to be an active and engaged member of the MPMOD Consortium by participating in shared governance of the national MPMOD Program and by providing complementary services to avoid costly and inefficient overlap between other MPMOD Centers. Finally, the Center will be an active participant in the MPMOD Vibrant Program and has proposed an innovative partnership between MPMOD Centers and Hispanic Serving Institutions (HSIs) in the 23-campus California State University (CSU) system.

国家肥胖和糖尿病活体模型代谢表型中心 (MPMOD) 在加州大学戴维斯分校 摘要——总体部分 根据疾病控制中心的数据，超过三分之一的美国成年人患有肥胖症 并发症（例如心脏病、中风、癌症），每年给美国经济造成超过 1500 亿美元的损失。 事实还不止于此：CDC 的最新数据显示 2 型糖尿病的发病率不断上升， 目前，约 11% 的美国成年人患有此病。 遗传因素、环境因素、食物和因素。 体力活动行为、慢性压力和同时发生的高风险疾病都与糖尿病和肥胖有关 在此背景下，进一步研究以更好地综合表型。 为了充分了解疾病的发病机制，特别需要与人类状况相关的小鼠模型 以及为遏制这一流行病蔓延制定战略提供信息的机制。 使用遗传、手术、人源化和其他类型的小鼠模型进行体内转化研究 现在尤其需要描述疾病的发病机制、机制和后果。 需要与人类代谢疾病的病理生理学相关，以便提供更有效的信息 诊断、治疗和预防策略，以促进这一努力并加速实现这些目标的进展。 为了实现这一目标，加州大学戴维斯分校提议建立国家小鼠模型代谢表型中心 肥胖和糖尿病 (MPMOD) 该中心将为糖尿病和肥胖研究社区提供服务。 获得专业和先进的资源来评估采用独特、复杂和 难以找到的测试和程序也将与有能力、经验丰富且可靠的 MPMOD 用户联系起来。 关于实验设计、测试选择、结果测量和解释的专家咨询和建议。 加州大学戴维斯分校 MPMOD 团队为研究界提供了坚实的服务基础：过去 10 年 多年来，加州大学戴维斯分校一直是 NIDDK 代谢小鼠表型中心 (MMPC) 的旗舰 联盟，提供活体小鼠的体内服务以及小鼠组织和血浆的体外分析 加州大学戴维斯分校的 MPMOD 中心将在这些成功的基础上继续发展。 以及我们强大的基础设施，可以提供许多新颖和创新的方法来解决现场的新问题 小鼠，利用更大的加州大学戴维斯分校科学企业和核心实验室为研究社区提供服务 提供高质量的体内代谢、生理和行为表型服务来表征 糖尿病、肥胖症和相关代谢紊乱的异质性、发病机制和后果。 加州大学戴维斯分校的 MPMOD 中心将由一个行政核心组成，提供行政、服务、 以及对中心的业务监督；动物核心，将进口和提供畜牧、护理和 许多特殊服务（例如 SPF 饲养、无菌小鼠管理、ABSL3 条件、 提交给中心的小鼠的显微外科能力、尸检和组织病理学； 代谢健康核心拥有丰富的资源和专业知识，可提供完善的代谢表型分析 测试加上创新方法（例如 PET 成像、连续血糖监测、先进的能量 平衡措施、异代谢组学）揭示宏量营养素代谢、能量摄入和 进食行为、能量消耗和代谢效率；以及生理学和行为核心 具有广泛而深入的专业知识和能力，可以提供对器官和组织的深入评估 全动物生理学（心血管、胃肠道、肾脏、呼吸系统、眼部和神经系统）和 运动行为、睡眠、学习和记忆、焦虑、抑郁和 每个核心都将有一位科学领导者和一位科学领导者。 共同领导者、核心协调员和技术专家进行大量的科学实验。 每个核心的顾问将提供有关实验设计、测试的专家建议 选择和数据解释，并根据要求提供新颖且复杂的测试和程序。 除了全面的测试和咨询之外，加州大学戴维斯分校 MPMOD 中心的一大优势 将与国际公认的新型鼠标生产和共享资产紧密合作 科学家当然可以派自己的小鼠进行测试，但除此之外他们还可以订购一个模型。 来自存储库（例如加州大学戴维斯分校 MMRRC、KOMP2 程序）的糖尿病或肥胖小鼠模型或具有 该中心为他们重新制作了相关的小鼠模型（例如基因改造、减肥手术模型）。 将以合理的成本向所有用户提供服务，无论用户是否 来自加州大学戴维斯分校内部或外部机构的项目收入将被再投资以开发新的测试。 技术、资助合作项目、支持费用减免以及补贴试点和可行性研究。 中心打算通过参与共享，成为 MPMOD 联盟的积极参与成员 国家 MPMOD 计划的治理，并通过提供补充服务来避免成本高昂和 其他 MPMOD 中心之间效率低下的重叠 最后，该中心将成为该项目的积极参与者。 MPMOD 活力计划并提议在 MPMOD 中心和 拥有 23 个校区的加州州立大学 (CSU) 系统中的西班牙裔服务机构 (HSI)。