Alternative Orosensory Signals Contributing to Sugar Taste

影响糖味的替代嗅觉信号

• 批准号: 10827641
• 负责人: Aracely Simental-Ramos
• 金额: $ 4.13万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10827641
• 关键词: Affect; Alpha-glucosidase; Amylases; Automobile Driving; Avidity; Behavior; Brain; Calories; Carbohydrates; Cells; Complex; Consummatory Behavior; Consumption; Data; Detection; Diabetes Mellitus; Diet; Disaccharides; Disease; Dopamine; Energy Intake; Enzymes; Epidemic; Feeding behaviors; Fiber; Fructose; Genetic; Glucokinase; Glucose; Glucose Transporter; Goals; Hydrolysis; Ingestion; Intake; Investigation; Knock-out; Knowledge; Laboratories; Learning; Ligands; Link; Maltose; Measures; Mediating; Mentors; Metabolic; Modeling; Monosaccharides; Mus; Obesity; Oral; Oral cavity; Pathway interactions; Peripheral; Photometry; Play; Process; Publishing; Reflex action; Research; Rewards; Role; Salivary; Sampling; Signal Transduction; Site; Starch; Structure of beta Cell of islet; Sucrose; Sweetening Agents; System; TRPM5 gene; Taste Bud Cell; Taste Buds; Taste Perception; Taste preferences; Testing; Training; United States; Work; detection of nutrient; detector; dietary; experience; experimental study; glucose sensor; glucosidase; glycemic control; hedonic; knock-down; mesolimbic system; motivated behavior; novel; preference; rapid detection; receptor; recruit; response; sensor; sugar; sweet receptor; sweet taste perception; taste transduction; testing access; western diet

PROJECT SUMMARY The increase of obesity and diabetes in the US is associated with the highly palatable sugar content of the western diet. The sweet taste receptor (T1R2+T1R3) is historically known to be the primary detector of sugars and non-caloric sweeteners. However, recent investigations from my mentor demonstrated that mice with genetic deletion of T1R2+T1R3 (or its downstream signaling mechanisms, TRPM5) still prefer the taste of glucose and/maltose, suggesting the involvement of other orosensory receptors. The Schier lab recently identified a glucose sensor in taste bud cells, glucokinase (GCK), that is upregulated with sugar exposure and is required to rapidly detect and develop preference for glucose over fructose in sweet-sensitive mice. However, GCK does not directly engage with maltose. Therefore I hypothesized that the α-glucosidase, maltase glucoamylase (MGAM) generates free glucose ligands that activate nearby sweet receptors and/or GCK-linked sensors to drive licking for maltose. My preliminary findings show that MGAM is upregulated in response to sugar exposure and that virogenetic knockdown of either MGAM or GCK reduces the hedonic appeal of maltose in sweet-sensitive mice. In this proposal, I aim to enhance this research by determining if MGAM- and GCK-linked behaviors depend on TRPM5-mediated taste transduction (Aim 1). With additional training in fiber photometry, I further aim to understand how the taste signals generated by metabolically distinct sugars recruit the mesolimbic dopaminergic reward system to guide ingestive decisions (Aim 2). The overarching goal of these studies is to understand and link glucosensing mechanisms to the central gustatory reward axis.

项目概要 美国肥胖和糖尿病的增加与高适口糖含量有关 西方饮食。甜味受体 (T1R2+T1R3) 历来被认为是糖的主要检测器 和无热量甜味剂。然而，我的导师最近的研究表明，具有遗传基因的小鼠 删除T1R2+T1R3（或其下游信号机制TRPM5）仍然更喜欢葡萄糖的味道 和/麦芽糖，表明其他口腔感觉受体的参与。席尔实验室最近发现了一种 味蕾细胞中的葡萄糖传感器葡萄糖激酶 (GCK)，它会随着糖暴露而上调，并且需要 快速检测并培养对甜味敏感的小鼠对葡萄糖而非果糖的偏好。然而，GCK 确实 不直接与麦芽糖结合。因此我推测α-葡萄糖苷酶、麦芽糖酶、葡糖淀粉酶 (MGAM) 产生游离葡萄糖配体，激活附近的甜味受体和/或 GCK 连接的传感器以驱动 舔麦芽糖。我的初步研究结果表明，MGAM 因糖暴露而上调，并且 MGAM 或 GCK 的病毒基因敲低会降低麦芽糖对甜味敏感的享乐吸引力 老鼠。在本提案中，我的目标是通过确定 MGAM 和 GCK 相关行为是否能够加强这项研究 依赖于 TRPM5 介导的味觉转导（目标 1）。通过光纤光度测定方面的额外培训，我进一步的目标是 了解代谢不同的糖产生的味觉信号如何招募中边缘 指导摄入决策的多巴胺能奖励系统（目标 2）。这些研究的总体目标是 了解葡萄糖传感机制并将其与中央味觉奖励轴联系起来。