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.

肥胖和糖尿病现场模型中的代谢表型（MPMOD）中的国家代谢表型（MPMOD） 在加州大学戴维斯分校 摘要 - 全部 根据疾病控制中心的数据，超过三分之一的美国成年人肥胖，遭受有关 并发症（例如，心脏病，中风，癌症），每年使美国经济损失超过1500亿美元。 事实并不止于此：CDC的最新数据显示2型糖尿病的发生率增加， 今天达到约11％的美国成年人口的患病率。遗传学，环境因素，食物和 体育锻炼行为，慢性压力和一致的高风险病毒均指向糖尿病和肥胖症 是异性起源的疾病。在这种情况下，高级研究更好地对表型进行全面的表型 特别需要与人类状况相关的小鼠模型才能充分理解疾病发病机理 以及为遏制这种不断增长的流行病的策略提供信息的机制。 使用遗传，外科手术，人性化和其他类型的小鼠模型在体内转化研究是 现在特别需要表征疾病发病机理，机制和后果。这些模型 需要与人类代谢疾病的病理生理学有关，以便更有效 诊断，治疗和预防策略。催化这一努力并加速进步 目标，加州大学戴维斯分校提出，建立了国家代谢表型的鼠标模型中心 肥胖和糖尿病（mpmod）。该中心将提供糖尿病和肥胖研究社区 访问专业和高级资源以评估使用独特，复杂和 难以找到的测试和程序。 MPMOD用户还将与能力，经验丰富的和 有关实验设计，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团队为研究社区提供了坚实的服务基础：在过去的10个 多年来，加州大学戴维斯分校在NIDDK代谢小鼠表型中心（MMPC）担任旗舰 财团，为活小鼠提供体内服务以及对鼠组织和血浆以及的体外分析 大研究社区的血清。加州大学戴维斯分校的MPMOD中心将取决于这些成功 以及我们强大的基础设施，提供许多新颖而创新的方法来解决现场的新问题 老鼠，借鉴更大的UC Davis Scientific Enterprise和Core Labs，为研究社区提供 在体内具有高质量的代谢，生理和行为表型服务，以表征 糖尿病，肥胖和相关代谢性疾病的异质性，发病机理和后果。 加州大学戴维斯分校的MPMOD中心将包括提供行政，服务的行政核心， 和中心的业务监督；将进口和提供饲养，关怀和的动物核心 众多特殊服务（例如，SPF饲养，Gnotobiotic Mouse Management，ABSL3条件， 小鼠的显微外科手术能力，死灵病和组织病理学）；一种新陈代谢和 代谢健康核心具有丰富的资源和专业知识，可提供成熟的代谢表型 测试以及创新方法（例如，宠物成像，连续的葡萄糖监测，复杂的能量 平衡测量，Xenometshromics），以揭示大量营养素代谢，能量摄入和 喂养行为，能量消耗和代谢效率；以及生理和行为核心 专业知识和能力的大量广度和深度，以提供对器官和器官的深入评估 全动物生理学（心血管，胃肠道，肾脏，呼吸道，眼和神经系统）和 神经行为行为，睡眠，学习和记忆，焦虑，抑郁和抑郁症的神经行为评估 压力和运动功能与糖尿病和肥胖有关。每个核心都会有科学领袖， 共同领导者，核心协调员和技术专家进行实验。许多科学 每个核心的顾问会员将提供有关实验设计，测试的专家建议 选择以及数据解释，并根据要求提供新颖而复杂的测试和程序。 除了综合测试和咨询之外，加州大学戴维斯分校MPMOD中心的主要优势 将与国际公认的资产有着密切的联系，用于生产和共享新型鼠标 疾病模型。科学家当然可以派遣自己的老鼠进行测试，但此外，他们可以订购 仅来自存储库的糖尿病的鼠标模型（例如，UC Davis MMRRC，KOMP2程序）或具有 该中心为它们提供了相关的小鼠模型（例如，一般改变，减肥手术模型）。 无论是否 从UC Davis内部或外部机构。该中心将重新投资计划收入以开发新的测试 技术，资助协作项目，支持费用摇动，并补贴试点和可行性研究。 中心打算通过参与共享来成为MPMOD财团的积极和参与的成员 国家mpmod计划的治理和提供完整服务以避免昂贵和 其他mpmod中心之间的无效重叠。最后，该中心将是活跃的参与者 MPMOD充满活力的计划，并提出了MPMOD中心之间的创新合作伙伴关系 加利福尼亚州立大学（CSU）系统的西班牙裔服务机构（HSIS）。