The incidence of diabetes in the United States is increasing rapidly as a result of the obesity epidemic. Mouse models have increased our understanding of the pathogenesis of diabetes and other metabolic diseases. The projects described in this grant utilize various genetic models to study the molecular mechanisms underlying energy homeostasis, and glucose and lipid metabolism. Core D provides accurate, timely and cost-effective phenotyping of mouse models generated by the Pis. Core D is directed by the PI of Project 3, Rex Ahima, who is also the director of the Penn Diabetes and Endocrinology Research Center (DERC) Mouse Phenotyping, Physiology and Metabolism Core. Core D supports the salary of a research specialist, supervised by the director Rex Ahima, to perform in vivo metabolic studies in mice. Core D uses state-of-the-art equipment and in vivo techniques. A Comprehensive Laboratory Animal Monitoring System (CLAMS) is used for assessment of food intake, drinking, energy expenditure, locomotor activity and sleep epochs. Nuclear Magnetic Resonance (NMR) and Dual Emission Xray Absorptiometry (DEXA) are used for assessment of body composition. Glucose homeostasis is evaluated with glucose and insulin tolerance tests, and insulin clamp and radioisotopic tracer kinetics. Core D also performs treadmill exercise, infrared thermography, blood pressure and heart rate monitoring, analysis of tissue chemistry, and tracer studies in isolated organs.