Metabolic Phenotyping in Live Models of Obesity and Diabetes

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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.