MECHANISMS OF PERIPHERAL FAT DETECTION

周围脂肪检测机制

基本信息

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
项目类别：
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

项目摘要

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。最主要的因素似乎是选择——多吃少运动，与肥胖相关的选择之一是选择高脂肪、高热量的饮食，尽管对脂肪摄入与肥胖之间的联系进行了大量研究。，对于化学感应机制知之甚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，以及这是如何产生的。此外，我们已经证明这些化学感觉机制是通过饮食和肥胖的发展来调节的，修订后的提案侧重于追求一个更有针对性的、单一的特定目标，旨在探索味觉如何发挥作用。对脂肪的反应由以下因素调节有新的和正在出现的数据证明了外围味觉系统的可塑性，但我们对系统如何随经验而变化的理解充其量是很差的，具体来说，我们将使用一种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以下假设：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种主要接受元件的变化，包括 CD36、GPR 120、GPR 84 和脂肪酸敏感元件。 DRK 通道。我们在前期广泛生成的初步数据表明，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。