Project Summary / Abstract – Core C. Metabolic, Physiological and Behavioral Phenotyping Core The purpose and primary goals of the Metabolic, Physiological and Behavioral (MPB) Phenotyping Core are to provide expert consultation, state-of-the art equipment, and technical services that are critical for the detailed in vivo metabolic and behavioral phenotyping of mouse models of obesity, diabetes, and associated disorders. A thorough understanding of the physiological responses to nutrients and environmental factors and of the pathophysiological mechanisms that contribute to diabetes and related metabolic diseases is required if we are to effectively combat these conditions. However, the resources and technology necessary to phenotypically probe whole animal models of altered glucose homeostasis and metabolism at a level that reveals basic underlying mechanisms of control are not available in most investigators’ laboratories. The MPB Core meets these needs through a comprehensive, convenient, and cost-effective menu of platforms that includes: 1) Glucose homeostasis and metabolic clamps (the Core performs hyperinsulinemic clamp studies including specialized analysis of metabolite storage and release in mice), 2) Whole animal metabolic assessment: The CLAMS and Promethion indirect calorimetry systems are used to examine metabolic rate, respiratory exchange ratio, food consumption, and locomotor activity in conventional mice or their germ-free counterparts, 3) In vivo lipid metabolism using 3H-labeled triglyceride, fatty acid, or glycerol for assessment of the tissue lipid incorporation and disposal or lipolysis. 4) In vivo steady-state stable isotope labeling of metabolites (the core performs bolus-continuous intravenous infusion to establish a steady-state of any given metabolite and provides samples to an independent Metabolomics Core at the university for further analyses of metabolic tracing or fluxes in tissues), 5) Automated blood/body fluids sampling and infusion utilizing a Culex/Empis platform to remotely collect serial samples and infuse substances to freely behaving, unstressed mice, 6) Mouse models of parabiosis, bariatric surgery, or germ-free mice. These models are provided by the Core and subsequent phenotyping can be performed with the combined resources of all the Cores in the Michigan MPMOD, 7) Exercise training and testing of running capacity including VO2max. 8) Basic behavioral tests to determine general locomotor activity, anxiety, exploration habits, or spatial learning in mouse models of metabolic dysfunction. 9) Ingestive behavior: Meal microstructure and reinforcing properties of dietary constituents are measured in either home-cage or operant-conditioning paradigms. 10) in vivo fiber photometry and optogenetic stimulation to monitor and manipulate activity in specific neuronal populations to assess their role in metabolism and behavior. The MPB Core also provides consultation and advice on experimental design, reliable data from a range of validated assays, essential data analysis relevant to the needs of multiple investigators and training opportunities in the established methodologies of the Core to researchers both at the University of Michigan and throughout the country.