ANIMAL PHYSIOLOGY CORE: Abstract The purpose of the Joslin Diabetes Research Center (DRC) Animal Physiology Core is to provide technically advanced physiological evaluation of rodents for the study of diabetes, obesity, and their associated complications. These studies provide a critical platform for extension of molecular discoveries to in vivo settings that provide critical insights for relevance to human metabolic diseases. The study of animal models is an integral part of Joslin Research. In addition to study of rats and established mouse models, Joslin DRC investigators have generated new strains of genetically engineered mice, the majority of which have been studied using the Animal Physiology Core. Services provided by the Animal Physiology enable investigators to quantify in vivo energy expenditure, activity and fuel utilization; body composition and bone density; arterial blood pressure and blood glucose levels; and hypoxia and hyperoxia. Equipment and expertise are available for in vivo and longitudinal animal imaging; controlled exposure to cold and thermoneutral temperatures using diurnal incubators; exercise using a rodent treadmill and activity wheel cages; assessment of muscle strength; and advanced retinal imaging and function. In addition, the Animal Physiology Core provides a Gnotobiotic Mouse Facility to study the role of the microbiome in metabolic diseases. Based on technological advances and needs of the DRC research base, the current application proposes substantial advances in the capabilities for quantification of energy expenditure and fuel utilization enabled by recent acquisition of a state-of the-art Sable Promethion System. The Animal Physiology Core provided services to 19 Joslin DRC Investigators and 11 outside Investigators in the past cycle. In addition, the Core educated investigators and fellows on the theoretical understanding of core procedures and data collection, consulted on study design, and provided hands-on training for some procedures and equipment. The Core has been essential in the publication of numerous papers, including many published in high impact journals such as Cell Metabolism, Nature Medicine, Nature Metabolism, Journal of Clinical Investigation, and Science Translational Medicine. Both institutional and DRC support for the Animal Physiology Core are substantial and enable Joslin’s Research Base to make physiologically relevant discoveries with potential for translation to improved treatments, prevention, and ultimately, cures for diabetes and related metabolic disorders.