Molecular Genetics of Fat Taste

摘要 味觉有助于提高生活质量和健康的饮食习惯，有助于认识食物中的营养成分。这个 负责传递糖(甜味)味道的潜在分子和细胞机制， 氨基酸(鲜味)和钠(咸味)已经被表征，但那些负责检测脂肪的是 有争议的。我们的初步研究表明，孤儿G蛋白偶联受体GPR113是一种 Gα蛋白GNA14转导GPR113型脂肪味觉信号。此外， 我们已经鉴定了一组表达GPR113和GNA14的T1R+味觉细胞，它们支持脂肪的味道。我们 建议阐明GPR113和GNA14在T1R+味觉细胞中的作用。在目标1中，我们将记录 脂肪味觉刺激在Gpr113基因敲除(KO)和GNA14中引起的行为和电生理反应 Ko老鼠。在目标2中，我们将使用基于细胞的分析来去变形GPR113，并评估 GNA14和T1Rs参与GPR113依赖的信号转导通路。在目标3中，我们将研究 我们假设的转录因子FOXA2调节脂肪味觉细胞的分化。知识 这项研究将提高我们对脂肪味道的理解，并为 把脂肪当作一种基本的味道。作为该项目的一部分，我们将建立一种基于细胞的检测方法来筛选GPR113 调节剂，这可能有助于开发脂肪味道增强剂，使我们能够减少脂肪含量 我们的饮食。

Summary Taste contributes to quality of life and healthy eating habits, aiding with the recognition of nutrients in food. The underlying molecular and cellular mechanisms responsible for transducing the taste of saccharides (sweet), amino acids (umami), and sodium (salty) have been characterized, but those responsible for detecting fat are controversial. Our preliminary studies indicate that an orphan G protein-coupled receptor, GPR113, is a bona fide fat taste receptor, and that the Gα protein GNA14 transduces the fat taste signal from GPR113. Moreover, we have identified a subset of T1R+ taste cells expressing GPR113 and GNA14 that support fat taste. We propose to elucidate the roles of GPR113 and GNA14 in T1R+ taste cells. In Aim 1, we will record the behavioral and electrophysiological responses elicited by fat taste stimuli in Gpr113 knockout (KO) and Gna14 KO mice. In Aim 2, we will use a cell-based assay to deorphanize GPR113 and evaluate the contribution of GNA14 and T1Rs to the GPR113-dependent transduction pathway. In Aim 3, we will study the role of a transcription factor, FOXA2, that we hypothesize regulates the differentiation of fat taste cells. Knowledge obtained from this research will improve our understanding of the taste of fat and provide an opportunity to consider fat as a basic taste. As part of the project, we will establish a cell-based assay to screen for GPR113 modulators, which could potentially help develop fat taste enhancers that will allow us to reduce fat contents in our diets.