The role of taste in amino acid appetite

味觉在氨基酸食欲中的作用

• 批准号: 8196794
• 负责人: Ivan E de Araujo
• 金额: $ 26.4万
• 依托单位: JOHN B. PIERCE LABORATORY, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8196794
• 关键词: Accounting; Address; Affect; Amino Acids; Animals; Area; Behavior; Behavioral; Brain; Carbohydrates; Consumption; Corpus striatum structure; Data; Desire for food; Disaccharides; Dopamine; Engineering; Food; Fructose; Galactose; Glucose; Glycine; Glycolysis Inhibition; Hyperphagia; Ingestion; Intake; Intravenous infusion procedures; Knockout Mice; Lactose; Macronutrients Nutrition; Maltose; Measurement; Metabolic; Metabolism; Monitor; Monosaccharides; Motivation; Mus; Nutrient; Physiological; Physiology; Play; Property; Proteins; Psychological reinforcement; Reaction; Regulation; Relative (related person); Research; Rewards; Rodent; Role; Shapes; Signal Transduction; Solutions; Stimulus; Stomach; Sucrose; Sugar Acids; Taste Perception; Testing; Work; absorption; base; extracellular; gastrointestinal; glucose analog; glucose metabolism; insight; neurochemistry; novel; oxidation; preference; public health relevance; research study; response; reward circuitry; sugar; sweet taste perception

DESCRIPTION (provided by applicant): This proposal addresses the critical question of which physiological mechanisms regulate the ability of an animal to select particular foods among a diverse array of macronutrients. The overall objective of this proposal is to examine the relative influence of post-absorptive, metabolic factors in contrast to gustatory input, on sugar and amino acid intake. More specifically, we will characterize a set of physiological responses that accompany amino acid vs. carbohydrate intake in both wild-type and genetically engineered taste-impaired mice. The physiological parameters to be monitored include the behavioral, calorimetric and neurochemical reactions that follow amino acid and carbohydrate consumption. Our central hypothesis states that the utilization of glucose as a metabolic fuel regulates nutrient preferences even when taste input is factored out. In other words, we hypothesize that the postingestive reward signals associated with sugars depend on the utilization of glucose as a cellular fuel. As a corollary, we specifically hypothesize that glucose utilization levels control extracellular dopamine concentration in striatum, given that nutrient preferences are ultimately regulated by dopamine signaling in this brain reward circuit. Testing this central hypothesis will involve employing behavioral, metabolic and neurochemical measurements in wild-type and Trpm5 knockout mice exposed to different carbohydrate and amino acid solutions. Importantly, by testing the glucose utilization hypothesis, the proposed project will provide novel data on how the metabolic and brain reward circuitry leads to the powerful motivation to consume sweet-tasting foods. The specific aims of this proposal are: 1 To characterize the role of glucose metabolism in postingestive reinforcement and 2 To characterize the role of glucose metabolism in the regulation of brain reward circuits. Consistent with our central hypothesis that glucose utilization favors carbohydrate intake over other nutrients, our preliminary studies allowed us to conclude that 1) KO mice show taste insensitivity to some several sugars and L-amino acids while displaying increased preferences for glucose compared to L-amino acid solutions in a way that is independent of taste input; 2) Glucose utilization rates are efficient predictors of sugar intake levels independently of taste input; 3) Sweet-impaired Trpm5 knockout mice attribute increased reward value to glucose when its ingestion counteracts the effects of glycolysis inhibition; 4) Dopamine levels in brain reward circuitries are sensitive to compounds that favor higher glucose utilization levels independently of orosensory stimulation; 5) Dopamine levels in these regions are negatively affected by glycolysis inhibition; 6) Trpm5 knockout mice display normal metabolization and absorption of ingested carbohydrate and proteins; in addition, differential behavioral responses to sugars and amino acids are not accounted for solely by gastrointestinal sensing and absorption. We believe that our studies will contribute to establishing an integrative physiology of sugar reward, an important and yet underrepresented area of research. PUBLIC HEALTH RELEVANCE: Uncovering sweet-independent reward signals favoring carbohydrate intake might significantly further our understanding on the reciprocal roles of gustatory and metabolic signals in stimulating the excessive consumption of sugars observed worldwide. In fact, there are several lines of evidence to suggest that currently undetermined sweetness-independent signals produced during glucose metabolism function to reinforce carbohydrate intake. Our work may provide new insights on the exact roles of taste quality and metabolism in sugar overconsumption.

描述（由申请人提供）：该提案解决了一个关键问题，即哪些生理机制调节动物在多种大量营养素中选择特定食物的能力。该提案的总体目的是检查出现后，代谢因子的相对影响，与糖输入，糖和氨基酸摄入相比。更具体地说，我们将表征一组伴随氨基酸与碳水化合物摄入量和基因工程性味觉影响的小鼠的生理反应。要监测的生理参数包括遵循氨基酸和碳水化合物消耗的行为，量热和神经化学反应。我们的中心假设指出，即使纳入味道输入，葡萄糖作为代谢燃料的利用也会调节营养偏好。换句话说，我们假设与糖有关的后奖励信号取决于将葡萄糖作为细胞燃料的利用。作为推论，我们特别假设葡萄糖利用水平控制纹状体中的细胞外多巴胺浓度，因为在该脑奖励回路中，营养偏好最终受到多巴胺信号传导的调节。测试此中心假设将涉及在暴露于不同碳水化合物和氨基酸溶液的野生型和TRPM5敲除小鼠中采用行为，代谢和神经化学测量。重要的是，通过检验葡萄糖利用假设，该提出的项目将提供有关代谢和脑奖励电路如何导致消费甜食食物的强大动机的新数据。该提案的具体目的是：1表征葡萄糖代谢在后增强中的作用，而2表征葡萄糖代谢在调节脑奖励电路中的作用。与我们的核心假设一致，即葡萄糖利用比其他营养素相对于其他营养素有利于碳水化合物的摄入量，我们的初步研究使我们得出结论：1）KO小鼠对几种糖和L-氨基酸的味道不敏感，而与L-Amino酸溶液相比，与L-Amino Aciduts相比，与L-Amino Acice溶液相比，与L-Amino酸溶液相比，与味觉独立的糖酸溶液相比，它具有增加的味道； 2）葡萄糖利用率是糖摄入水平的有效预测因子，而不是味道输入； 3）当摄入的葡萄糖抵消糖酵解抑制的作用时，甜味的TRPM5敲除小鼠将奖励值归因于葡萄糖； 4）大脑奖励回路中的多巴胺水平对有利于葡萄糖利用水平的化合物敏感，独立于口感刺激； 5）这些区域的多巴胺水平受糖酵解抑制作用负面影响； 6）TRPM5敲除小鼠表现出正常的代谢和摄入的碳水化合物和蛋白质的吸收；另外，仅仅仅通过胃肠道感应和吸收来解释对糖和氨基酸的差异行为反应。我们认为，我们的研究将有助于建立糖奖励的综合生理学，这是一个重要但人数不足的研究领域。 公共卫生相关性：发现有利于碳水化合物摄入的甜蜜独立的奖励信号可能会进一步进一步了解我们对味觉和代谢信号在刺激全球观察到的糖的过度消费方面的相互作用的理解。实际上，有几条证据表明，目前在葡萄糖代谢功能期间产生的不确定的非依赖性信号以增强碳水化合物的摄入量。我们的工作可能会提供有关糖品质质量和代谢在糖分过量中的确切作用的新见解。