Molecular Genetics of Fat Taste

脂肪味觉的分子遗传学

基本信息

批准号：
10304173
负责人：
ICHIRO MATSUMOTO
金额：
$ 32.97万
依托单位：
MONELL CHEMICAL SENSES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-12-01 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10304173
关键词：
Amino Acids Animals Behavioral Biochemical Biological Assay Cell Differentiation process Cells Data Detection Diet Diet Habits Dietary Oils Ectopic Expression Electrophysiology (science)Energy-Generating Resources Enhancers Esthesia Fatty Acids Fatty acid glycerol esters Food Food Selections G-Protein-Coupled Receptors GNA14 gene GTP-Binding Protein alpha Subunits GTP-Binding Protein alpha Subunits, Gs Genes Genetically Engineered Mouse Glossopharyngeal nerve structure Health Healthy Eating Image In Vitro Knock-in Knock-out Knockout Mice Knowledge Lead Light Lipids LoxP-flanked allele Mediating Molecular Molecular Chaperones Molecular Genetics Nature Nerve Nonesterified Fatty Acids Nutrient Obesity Orphan Pathway interactions Population Proteins Quality of life Research Role Signal Transduction Signaling Molecule Sodium Sweetening Agents System Taste Buds Taste Perception Testing Transducers Transgenic Mice Wild Type Mouse Work alpha-gustducin base behavior test behavioral response dietary gain of function improved in vivo insight interest loss of function mutant receptor response somatosensory sweet taste perception taste stimuli transcription factor

项目摘要

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.

概括味道有助于提高生活质量和健康的饮食习惯，有助于识别食物中的营养成分。负责转导糖类味道（甜）的潜在分子和细胞机制，氨基酸（鲜味）和钠（咸味）已被表征，但负责检测脂肪的那些是我们的初步研究表明，孤儿 G 蛋白偶联受体 GPR113 是一种真正的受体。脂肪味觉受体，并且 Gα 蛋白 GNA14 转导来自 GPR113 的脂肪味觉信号。我们已经鉴定出表达 GPR113 和 GNA14 的 T1R+ 味觉细胞子集，支持脂肪味觉。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 Gpr113 敲除 (KO) 和 Gna14 中脂肪味觉刺激引起的行为和电生理反应在目标 2 中，我们将使用基于细胞的测定来使 GPR113 去孤儿化并评估 GPR113 的贡献。 GNA14 和 T1R 对 GPR113 依赖性转导途径的影响在目标 3 中，我们将研究 GNA14 和 T1R 的作用。我们调节的转录因子 FOXA2 调节脂肪味觉细胞的分化。这项研究获得的成果将提高我们对脂肪味道的理解，并提供一个机会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。