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

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.