Molecular Genetics of Fat Taste

脂肪味觉的分子遗传学

• 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
• 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

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.

总结 味觉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。的 负责转导甜味的潜在分子和细胞机制， 氨基酸（鲜味）和钠（咸味）已经被表征，但负责检测脂肪的是 争议我们的初步研究表明，孤儿G蛋白偶联受体GPR113是一种有效的抗肿瘤药物。 而Gα蛋白GNA14则从GPR113中转导脂肪味觉信号。此外，委员会认为， 我们已经鉴定了表达支持脂肪味的GPR113和GNA14的T1R+味觉细胞的亚群。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 在Gpr113敲除（KO）和Gna14中由脂肪味觉刺激引起的行为和电生理反应 KO小鼠。在目的2中，我们将使用基于细胞的测定来使GPR113去活化并评估GPR113的贡献。 GNA14和T1R与GPR113依赖性转导途径的相互作用。在目标3中，我们将研究 转录因子，FOXA 2，我们假设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，并提供一个机会， 将脂肪视为基本口味。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