Project Summary The Mouse Metabolic Physiology Core and its two subcores, the Metabolic Regulation Subcore and the Body Weight Regulation Subcore, provide investigators both guidance on experimental design and use of state-of- the-art techniques to assess genetic and environmental determinants of insulin action, substrate metabolism, and energy balance in vivo. The experienced faculty and highly skilled staff of this Core have a 20-year history of performing complex procedures to study metabolism in healthy, unstressed mice and have been at the forefront of development, standardization, implementation, and dissemination of new concepts and techniques to study mouse models of metabolic diseases. In the present application, the Mouse Metabolic Physiology Core delivers critically needed mouse-related services to investigators outside of Vanderbilt. Skilled mouse surgeons perform difficult surgeries such as catheter, brain cannula, and brain probe implantations, as well as bariatric surgery and islet transplantation. Experienced staff perform complex experiments such as metabolic flux analyses under conditions such as those created by a glucose clamp or exercise. Measurements of energy balance components and assessment of reward/motivated behavior allow for the physiological and behavioral determinants of body weight to be determined in mouse models of metabolic disease. This Core merges techniques so that oxygen uptake, carbon dioxide output, energy expenditure, activity and feeding behavior are measured simultaneously with studies of metabolism using indwelling catheters or neural regulation using implanted cannula and fiber optic probes. Experience at Vanderbilt over the past 5 years predicts robust use of this Core. The Mouse Metabolic Physiology Core participates in important educational programs for the diabetes community, including a weeklong course that has been given 20 times over 19 years focusing on surgical and experimental techniques necessary to perform glucose clamps in mice. This Core supports the Vanderbilt Vibrant Program by providing necessary time and resources to investigators from underrepresented populations or institutions and early-career investigators. In summary, the Core facilitates diabetes, obesity, and metabolism research by providing novel services that are feasible at few other institutions to investigators outside of Vanderbilt.