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.

在美国和世界范围内，肥胖症的发病率持续上升，心血管疾病、糖尿病和其他相关疾病的相关问题也相应增加。 大部分肥胖是由饮食引起的，并且与西方平均饮食中的高脂肪含量有关。 尽管脂肪摄入与肥胖之间的联系已被广泛研究，但人们对身体识别膳食脂肪的机制知之甚少，更不知道这些机制如何相互关联并有助于调节膳食脂肪摄入。我们最近证明，必需脂肪酸为味觉系统提供了显着的线索，这与首次详细描述其“脂肪的味道”相一致。 此外，我们在初步实验中表明，这种脂肪酸介导的延迟整流 K+ 通道抑制可能是身体识别膳食脂肪的通用系统。 该项目结合了电生理学、分子生物学和行为测定，其总体目标是识别和表征味觉系统的反应性及其在帮助塑造偏好脂肪和避免脂肪的大鼠品系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品系中解决以下 3 个具体目标： 目标 1：确定味觉受体细胞从脂肪偏好和回避率到脂肪酸的反应性、其作用机制以及这种反应性与脂肪酸的关系膳食脂肪偏好。 这将测试以下一般假设：这两种菌株中的差异脂肪反应性是由于 K+ 通道表达的差异造成的，并鉴定脂肪反应元件。 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分析来测试以下假设：必需脂肪酸被味觉系统识别，并且它们可以增强对其他促味剂的反应。我们还将确定具有不同饮食脂肪偏好的大鼠在味觉细胞水平上观察到的差异如何与行为相关。 目标 3：确定味觉系统在帮助塑造营养（脂肪）摄入量方面可能发挥的作用。 我们将分析各种饮食情况下的饮食行为，以检验脂肪酸介导的味觉细胞激活有助于控制脂肪摄入的假设。 这些研究将增进我们对脂肪信号传导机制及其与饮食偏好的关系的理解。此外，它还可以为新的治疗靶点提供见解，该靶点可用于调节脂肪摄入，并最终控制饮食引起的肥胖及其相关疾病。