Mechanisms of alimentary chemosensation

描述（由申请人提供）：味觉系统的一个关键功能是检测营养物质、毒素和变质指标，从而在动物摄入食物之前向动物提供有关食物质量和营养价值的关键信息。检测和辨别味觉刺激的能力对健康和生存至关重要，并能驱动摄食行为。因此，在营养需求和代谢状态下调节味觉功能的生理机制可以优化摄食决策，直接影响人类健康。尽管味觉系统对食物偏好、食物摄入和代谢稳态有重要影响，但人们对味觉功能和代谢之间的生理机制知之甚少。我们的实验室和其他人最近的发现表明，味觉和胃肠道系统利用一个由受体、信号分子和激素组成的共同分子工具包来检测营养物质和其他化学物质。这与味觉功能在维持代谢稳态中的作用是一致的，并表明感觉功能可能在代谢状态的背景下被调节。更深入地了解代谢激素和味觉感觉器官之间的相互作用，将对理解代谢性疾病的病因学产生重要影响。这个项目将在三个方面研究味觉和激素系统之间的相互作用。在目的1中，我们将研究味觉受体和味觉受体变异对葡萄糖稳态维持的贡献。在Aim 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，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Aim 3中，我们将研究GLP-1、胰高血糖素和另一种激素瘦素相互影响味觉功能的能力。总之，这些研究将为味觉、营养和代谢之间的相互作用提供重要的新见解，并可能对代谢性疾病（如肥胖、2型糖尿病和代谢综合征）产生广泛的影响。尽管味觉系统对食物偏好、食物摄入和代谢稳态有重要影响，但人们对味觉功能和代谢之间的生理机制知之甚少。我们的实验室和其他人最近的研究结果表明，味觉对维持代谢稳态很重要，并且味觉功能可能在代谢状态的背景下被调节。这些研究将探讨味觉和激素系统之间的相互作用，为味觉、营养和代谢之间的相互作用提供重要的新见解，这可能对肥胖、2型糖尿病和代谢综合征等代谢性疾病有广泛的影响。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE 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 taste is important for the maintenance of metabolic homeostasis and that taste function may be modulated in the context of metabolic status. The proposed studies will investigate the interactions between taste and hormonal systems, providing important new insights into the interplay between taste, nutrition and metabolism that could have broad implications for metabolic diseases such as obesity, Type 2 diabetes mellitus, and the metabolic syndrome.