MECHANISMS OF PERIPHERAL FAT DETECTION

周围脂肪检测机制

• 批准号: 7730887
• 负责人: TIMOTHY A. GILBERTSON
• 金额: $ 34.75万
• 依托单位: UTAH STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7730887
• 关键词: Anterior; Area; Behavior; Behavioral Assay; Biological; Biological Assay; CD36 Antigens; CD36 gene; Cardiovascular Diseases; Cells; Cues; Data; Detection; Development; Diabetes Mellitus; Diet; Dietary Fats; Disease; Eating; End stage renal failure; Exercise; Fat Substitutes; Fatty Acids; Fatty acid glycerol esters; G-Protein-Coupled Receptors; Gene Expression; Genes; Goals; Incidence; Indium; Intake; Investigation; Ion Channel; Laboratories; Lead; Link; Measures; Molecular; Mus; Nonesterified Fatty Acids; Nutrient; Nutritional; Nutritional status; Obesity; Oral cavity; Pathway interactions; Peripheral; Polyunsaturated Fatty Acids; Potassium Channel; Property; Receptor Cell; Regulation; Research; Resistance; Rodent; Signal Pathway; System; Taste Perception; Testing; Texture; Time; Tissues; Tongue; Treatment Protocols; Well in self; base; design; experience; feeding; interdisciplinary approach; meetings; multidisciplinary; novel; nutrition; receptor; receptor expression; receptor function; response; somatosensory

The incidence of obesity worldwide continues to escalate with the spread of the Western diet and with it there has been a corresponding increase in cardiovascular disease, diabetes, end-stage renal disease and other obesity-related disorders. Of all the causes for obesity, the predominant one seems to be choice - the choice to eat more and exercise less. One of the choices that has been linked with obesity has been the selection of a high fat, calorically dense diet. Despite much research on the link between fat intake and obesity, relatively little is known about the chemosensory mechanisms that underlie the taste of fat and how these mechanisms might contribute to dietary fat intake. Our previous research has identified differences in how the taste systems in obesity-prone and –resistant rodents respond to fatty acids, a cue for dietary fat, and how this was correlated to differences in gene expression and receptor function. Moreover, we have demonstrated that these chemosensory mechanisms are modulated by diet and the development of obesity. The revised proposal focuses on pursuing a more focused, single remaining specific aim that seek to explore how the gustatory response to fat is modulated by dietary experience. There is new and emerging data that argues to the plasticity of the peripheral taste system, yet our understanding of how the system changes in relation to experience is poor at best. Specifically, we will use an approach including a multidisciplinary approach to answer the following question: 1. Is the fatty acid transduction pathway modulated by diet? Our multidisciplinary approach analyzing genes through behavior will be used to test the hypothesis that fat receptor expression in taste cells is altered during high fat feeding in a manner that results in an increased responsiveness to fatty acids. Following high fat dietary regimens, molecular, cell-based and behavioral assays will be performed to measure changes in four primary receptive elements in the fatty acid signaling pathway, including CD36, GPR 120, GPR 84 and fatty acid-sensitive DRK channels. Our extensive preliminary data generated in the previous period would argue that these are the primary components of the pathway that underlies the ability of the gustatory system to recognize and respond to free fatty acids.

随着西方饮食的传播，全世界肥胖的发病率持续上升，心血管疾病、糖尿病、终末期肾病和其他与肥胖相关的疾病也相应增加。在所有导致肥胖的原因中，最主要的原因似乎是选择——选择多吃少运动。与肥胖相关的选择之一是选择高脂肪、高热量饮食。尽管对脂肪摄入与肥胖之间的联系进行了大量研究，但人们对脂肪味道背后的化学感觉机制以及这些机制如何影响膳食脂肪摄入的了解相对较少。我们之前的研究已经确定了易肥胖和抗肥胖啮齿动物的味觉系统对脂肪酸（膳食脂肪的暗示）的反应差异，以及这与基因表达和受体功能差异的关系。此外，我们已经证明这些化学感应机制受到饮食和肥胖的发展的调节。修订后的提案侧重于追求一个更有针对性、单一的具体目标，旨在探索饮食经验如何调节对脂肪的味觉反应。有新出现的数据证明了外围味觉系统的可塑性，但我们对该系统如何随体验而变化的理解充其量也很差。具体来说，我们将使用包括多学科方法在内的方法来回答以下问题： 1. 脂肪酸转导途径是否受饮食调节？我们通过行为分析基因的多学科方法将用于检验这样的假设：味觉细胞中的脂肪受体表达在高脂肪喂养期间发生改变，从而导致对脂肪酸的反应性增加。在高脂肪饮食方案之后，将进行分子、细胞和行为测定，以测量脂肪酸信号通路中四个主要感受元件的变化，包括 CD36、GPR 120、GPR 84 和脂肪酸敏感 DRK 通道。我们在前一时期产生的大量初步数据表明，这些是味觉系统识别和响应游离脂肪酸能力的途径的主要组成部分。