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.

项目摘要 美国肥胖症和糖尿病的增加与葡萄酒中高可口的糖含量有关。 西方饮食。甜味受体（T1R2 + T1R3）在历史上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， T1R2 + T1R3（或其下游信号传导机制，TRPM5）的缺失仍然偏好葡萄糖的味道 和/麦芽糖，表明其他orosensory受体的参与。希耶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），随着糖暴露而上调， 快速检测并在甜味敏感的小鼠中发展对葡萄糖的偏好。然而，GCK 不直接与麦芽糖接触。因此我假设α-葡萄糖苷酶麦芽糖酶葡萄糖淀粉酶 （MGAM）产生游离葡萄糖配体，其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是上调响应糖暴露， MGAM或GCK的病毒发生学敲低降低了甜味敏感型中麦芽糖的享乐吸引力， 小鼠在这个建议中，我的目标是通过确定是否MGAM和GCK相关的行为来加强这项研究 依赖于TRPM5介导的味觉传导（Aim 1）。通过对光纤测光的额外培训，我进一步瞄准了 为了了解不同代谢糖产生的味觉信号如何招募中脑边缘系统， 多巴胺能奖励系统，以指导摄食决定（目的2）。这些研究的首要目标是 了解并将葡萄糖感应机制与中央味觉奖赏轴联系起来。