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; 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 美国肥胖和糖尿病的增加与高度可口的糖含量有关 西方饮食。甜味受体（T1R2+T1R3）在历史上是糖的主要检测器 和非热甜味剂。但是，我心理的最近调查表明，遗传的小鼠 删除T1R2+T1R3（或其下游信号传导机制，TRPM5）仍然更喜欢葡萄糖的味道 和/麦芽糖，表明其他口感受体的参与。 Schier Lab最近确定了 味蕾葡萄糖酶（GCK）中的葡萄糖传感器，随着糖暴露而更新，需要 在甜敏感小鼠中，快速检测并发展对葡萄糖而不是果糖的偏爱。但是，GCK确实如此 不直接与麦芽糖互动。因此，我假设α-葡萄糖苷酶，麦芽糖酶葡萄糖酰基酶 （MGAM）生成免费的葡萄糖配体，该配体激活附近的甜蜜接收器和/或GCK连锁传感器以驱动 舔麦芽糖。我的初步发现表明，MGAM是根据糖暴露和 MGAM或GCK的病毒式敲低可降低甜敏感中麦芽糖的享乐外观 老鼠。在此提案中，我旨在通过确定MGAM和GCK连接行为来增强这项研究 取决于TRPM5介导的味觉转移（AIM 1）。通过纤维光度法进行额外的培训，我进一步瞄准 要了解由代谢不同的糖产生的味道如何募集中唇胶质 多巴胺能奖励系统指导摄入决策（AIM 2）。这些研究的总体目标是 理解并将糖化机制与中央味道奖励轴联系起来。