Mechanisms of alimentary chemosensation

项目摘要 味觉系统的一个关键功能是检测营养物质、毒素和腐败指标， 从而为动物提供关于食物质量和营养价值的关键信息 在它被吞下之前。检测和辨别味觉刺激的能力对健康至关重要 和生存，并能驱动摄食行为。因此， 在营养需求和代谢状态的背景下调节味觉功能可以优化 消化决定，直接影响人类健康。尽管味觉系统 影响食物偏好、食物摄入和代谢稳态， 人们对味觉功能和新陈代谢之间的联系机制知之甚少。最近的调查结果 我们的实验室和其他人的研究表明，味觉和胃肠道系统利用一种 用于检测营养物质的受体、信号分子和激素的通用分子工具包 和其他化学品。这与味觉功能在维持胃肠道功能中的作用是一致的。 代谢稳态，并表明感觉功能可能是调制的背景下， 代谢状态更好地理解代谢激素和 味觉感觉器官对于理解 代谢性疾病的病因学。这个项目将研究味觉和 激素系统有三个目标。在目标1中，我们将研究味觉感受器的贡献 和味觉受体变体来维持葡萄糖稳态。在目标2中，我们 表征在味觉细胞和消化系统中表达的两种激素的作用， 胰高血糖素样肽-1（GLP-1）和胰高血糖素在味觉敏感性调节中的作用。在目标3中， 我们将检查GLP-1、胰高血糖素和另一种激素瘦素影响各自的能力 其他对味觉功能的影响。总之，这些研究将提供重要的新见解， 味觉、营养和新陈代谢之间的相互作用，可能对 代谢疾病，如肥胖症、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.