PROJECT SUMMARY/ABSTRACT Rodents offered a cafeteria choice of two or more “supermarket” foods gain substantially more weight than if fed only one such food. This “cafeteria-feeding” model captures aspects of human obesity that are missing from other rodent models, but the use of prepared human foods adds complexity that precludes meaningful analysis and interpretation. We have developed a simpler and more rigorous model to investigate the causes of the heightened obesity imparted by cafeteria feeding. Mice offered a choice between a high-carbohydrate, low-fat diet and an equicaloric low-carbohydrate, high-fat diet gain substantially more weight than do mice fed either diet alone. To characterize and establish this new model, we will determine the range of proportions of carbohydrate and fat that support the extra weight gain (Aim 1), investigate whether various sources of carbohydrate and fat are equally effective (Aim 2), determine whether mice actively select carbohydrate and fat diets that maximize their obesity (Aim 3), and investigate the temporal aspects of the carbohydrate-fat interaction by switching mice between high-carbohydrate and high-fat diets at various intervals, including between successive meals and within meals (Aim 4). These and related follow-up experiments will give insight into the causes of cafeteria-feeding obesity, and set the stage for the identification of the underlying physiological mechanisms. The mouse cafeteria-feeding paradigm has obvious direct parallels to the human experience. As such, this project will yield an animal model that can be exploited to investigate the physiological, neural and genetic mechanisms responsible for the “extra” obesity caused by cafeteria feeding. It will thus establish a more faithful model of human obesity than those currently available.