MECHANISMS OF PERIPHERAL FAT DETECTION

周围脂肪检测机制

• 批准号: 6326418
• 负责人: TIMOTHY A. GILBERTSON
• 金额: $ 33.23万
• 依托单位: UTAH STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6326418
• 关键词: behavioral /social science research tag; dietary lipid; free fatty acids; genetic strain; laboratory rat; molecular cloning; nutrient intake activity; nutrition related tag; obesity; polymerase chain reaction; potassium channel; preference; taste; taste buds; voltage /patch clamp

The incidence of obesity in the United States and worldwide continues to escalate and with it there is a corresponding increase in the associated problems of cardiovascular disease, diabetes, and other related disorders. Much of the obesity is dietary induced and is correlated with high-fat content in the average Western diet. Though the link between fat intake and obesity has been extensively studied, there is comparatively little known about the mechanisms by which the body recognizes dietary fat and even less known about how these mechanisms correlate and contribute to the regulation of dietary fat intake. We have recently demonstrated that the essential fatty acids provide salient cues to the gustatory system, consistent with this representing the first detailed description of their being a "taste of fat". Moreover, we have shown in preliminary experiments that this fatty acid-mediated inhibition of delayed rectifying K+channels may be a universal system by which the body recognizes dietary fat. The overall aim of this project combining electrophysiology, molecular biology and behavioral assays is to identify and characterize the responsiveness of taste system and its role in helping to shape the dietary preferences of strains of fat-preferring and fat-avoiding rats. To accomplish these goals we will address the following 3 specific aims in these two rat strains: AIM 1: To determine the responsiveness of taste receptor cells from fat-preferring and avoiding rate to fatty acids, their mechanism of action and how this responsiveness correlates with dietary fat preference. This will test the general hypothesis that the differential fat responsiveness in these two strains is due to difference in K+ channel expression and identify the fat responsive elements. AIM 2: To determine the effectiveness of fatty acids as gustatory stimuli. We will use a series of behavioral assays to test the hypotheses that essential fatty acids are recognized by the taste system and that they may enhance the response to other tastants. We will also determine how the differences seen at the taste cell level between rats with different dietary fat preferences is correlated with behavior. AIM 3: To determine the role the taste system may play in helping to shape nutrient (fat) intake. We will analyze eating behavior in the presence of various diets to test the hypothesis that the fatty acid mediated taste cell activation contributes to the control of fat intake. These studies will advance our understanding the mechanisms of fat signaling and their relationship to dietary preferences. Moreover, it may provide insights into a novel therapeutic targets that can be used in the regulation of fat intake and, ultimately, in the control of dietary-induced obesity and its related disorders.

美国和全球肥胖的发生率继续升级，随之而来的是心血管疾病，糖尿病和其他相关疾病的相关问题的相应增加。 肥胖症的大部分是饮食诱发的，并且与平均西方饮食中的高脂含量相关。 尽管已经对脂肪摄入与肥胖之间的联系进行了广泛的研究，但人们对人体识别饮食脂肪的机制鲜为人知，甚至对这些机制如何相关并有助于调节饮食脂肪的摄入量的机制。我们最近证明，必需的脂肪酸为味道系统提供了显着的提示，这与这是对它们的“脂肪味道”的第一个详细描述一致的。 此外，我们在初步实验中表明，这种脂肪酸介导的抑制延迟矫正K+通道的抑制可能是人体识别饮食脂肪的通用系统。 该项目结合电生理学，分子生物学和行为测定的总体目的是识别和表征味觉系统的反应性及其在帮助塑造脂肪偏爱和避免脂肪大鼠的饮食偏好方面的作用。为了实现这些目标，我们将在这两种大鼠菌株中解决以下3个特定目标：目标1：确定味觉受体细胞的反应性，从脂肪偏爱和避免对脂肪酸的速率，它们的作用机理以及这种反应能力与饮食脂肪偏好相关。 这将检验以下一般假设：这两种菌株中的差异反应性是由于K+通道表达的差异并确定脂肪响应元素。 目标2：确定脂肪酸作为味觉刺激的有效性。 我们将使用一系列行为测定法来测试味觉系统认识到必需脂肪酸的假设，并且它们可能会增强对其他味道的反应。我们还将确定具有不同饮食脂肪偏爱的大鼠之间味觉细胞水平的差异与行为相关。 目标3：确定味觉系统在帮助塑造营养（脂肪）摄入量中的作用。 我们将在存在各种饮食的情况下分析饮食行为，以检验以下假设：脂肪酸介导的味觉细胞激活有助于控制脂肪摄入。 这些研究将促进我们了解脂肪信号传导的机制及其与饮食偏好的关系。此外，它可以提供对可用于调节脂肪摄入的新型治疗靶标的见解，并最终控制饮食诱发的肥胖症及其相关疾病。