Causes of cafeteria-feeding obesity

项目概要/摘要 啮齿动物在自助餐厅里选择两种或两种以上的“超市”食物， 只吃一种这样的食物。这种“饮食喂养”模式捕捉到了人类肥胖所缺失的方面 从其他啮齿动物模型，但使用准备好的人类食物增加了复杂性，排除了有意义的 分析和解释。我们已经开发了一个更简单，更严格的模型来调查原因 自助餐导致的肥胖加剧老鼠可以在高碳水化合物， 低脂肪饮食和等量低碳水化合物、高脂肪饮食的小鼠体重增加显著高于喂食 或者单独节食。为了表征和建立这个新模型，我们将确定 碳水化合物和脂肪，支持额外的体重增加（目标1），调查是否各种来源的 碳水化合物和脂肪同样有效（目的2），确定小鼠是否主动选择碳水化合物和脂肪 饮食，最大限度地增加他们的肥胖（目标3），并调查的时间方面的碳水化合物-脂肪 通过在不同的时间间隔在高碳水化合物和高脂肪饮食之间切换小鼠， 连续两餐之间和餐内（目标4）。这些和相关的后续实验将提供洞察力 的原因，并设置阶段，为确定潜在的 生理机制。老鼠吃蔬菜的模式与人类有着明显的直接相似之处 体验.因此，该项目将产生一种动物模型，可用于研究 生理、神经和遗传机制导致自助餐引起的“额外”肥胖。 因此，它将建立一个比目前可用的更可靠的人类肥胖模型。

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.