Mechanisms of alimentary chemosensation

项目摘要 味觉系统的一个关键功能是检测营养、毒素和腐烂的指示物， 从而为动物提供有关食物质量和营养价值的重要信息 在它被摄取之前。检测和辨别味觉刺激的能力对健康是必不可少的 和生存，并可以驱动摄取行为。因此，生理机制 根据营养需求和代谢状态调整味觉功能可以优化 胃肠道决定和直接影响人类健康。尽管味觉系统在批判性地 影响食物偏好、食物摄入量和代谢动态平衡，生理 将味觉功能和新陈代谢联系起来的机制还知之甚少。最新发现 来自我们实验室和其他人的研究表明，味觉和胃肠系统利用 检测营养物质的受体、信号分子和激素的通用分子工具包 和其他化学物质。这与味觉功能在维护中的作用是一致的 代谢动态平衡，并提示感觉功能可能在 代谢状态。更好地理解代谢激素和 味觉感觉器将对理解 代谢性疾病病因学。这个项目将调查味觉和味觉之间的相互作用 荷尔蒙系统有三个目标。在目标1中，我们将研究味觉受体的作用。 和味觉受体变异，以维持葡萄糖的动态平衡。在目标2中，我们将 描述在味觉细胞和消化系统中表达的两种激素的作用， 胰升糖素样肽-1(GLP-1)和胰高血糖素，在调节味觉敏感度。在《目标3》中， 我们将检测GLP-1、胰高血糖素和另一种荷尔蒙瘦素对它们的影响能力 他人对味觉功能的影响。总之，这些研究将提供重要的新见解 味道、营养和新陈代谢之间的相互作用，可能会对 代谢性疾病，如肥胖、2型糖尿病和代谢综合征。

Project Summary A key function of the gustatory system is to detect nutrients, toxins and indicators of spoilage, thus providing critical information to the animal about the quality and nutritional value of food before it is ingested. The ability to detect and discriminate taste stimuli is essential for health and survival, and can drive ingestive behaviors. Therefore, physiological mechanisms that modulate taste function in the context of nutritional needs and metabolic status could optimize ingestive decisions and directly impact human health. Although the gustatory system critically influences food preference, food intake and metabolic homeostasis, the physiological mechanisms that link taste function and metabolism are poorly understood. Recent findings from our laboratory and others suggest that the gustatory and gastrointestinal systems utilize a common molecular toolkit of receptors, signaling molecules and hormones to detect nutrients and other chemicals. This is consistent with a role for taste function in the maintenance of metabolic homeostasis and suggests that sensory function may be modulated in the context of metabolic status. A greater understanding of the interactions between metabolic hormones and the gustatory sensory apparatus would have important consequences for understanding the etiology of metabolic disease. This project will investigate the interactions between taste and hormonal systems in three Aims. In Aim 1, we will examine the contribution of taste receptors and taste receptor variants to the maintenance of glucose homeostasis. In Aim 2, we will characterize the role of two hormones expressed in taste cells and in the digestive system, glucagon-like peptide-1 (GLP-1) and glucagon, in the modulation of taste sensitivity. In Aim 3, we will examine the ability of GLP-1, glucagon and another hormone, leptin, to influence each other's effects on taste function. Together, these studies will offer important new insights into the interplay between taste, nutrition and metabolism and could have broad implications for metabolic diseases such as obesity, Type 2 diabetes mellitus, and the metabolic syndrome.