MECHANISMS OF PERIPHERAL FAT DETECTION

周围脂肪检测机制

• 批准号: 7623683
• 负责人: TIMOTHY A. GILBERTSON
• 金额: $ 27.74万
• 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 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7623683
• 关键词: Behavior; Behavioral Assay; Biological Assay; CD36 Antigens; CD36 gene; Carbohydrates; Cardiovascular Diseases; Cells; Class; Cues; Data; Detection; Development; Diabetes Mellitus; Diet; Dietary Fats; Disease; Eating; Electrophysiology (science); Elements; End stage renal failure; Exercise; Fatty Acids; Fatty acid glycerol esters; G-Protein-Coupled Receptors; Gene Expression; Genes; Goals; Image; Incidence; Intake; Ion Channel; Laboratories; Link; Longevity; Macronutrients Nutrition; Measures; Modeling; Molecular; Molecular Biology; Neurons; Nonesterified Fatty Acids; Numbers; Nutritional; Obesity; Oral cavity; Pathway interactions; Perception; Performance; Peripheral; Polymerase Chain Reaction; Polyunsaturated Fatty Acids; Potassium Channel; Property; Proteins; Rattus; Receptor Cell; Research; Resistance; Rodent; Role; Series; Specificity; System; Taste Perception; Testing; Texture; Time; Tissues; Trigeminal System; Unsaturated Fatty Acids; base; cell type; day; experience; feeding; immunocytochemistry; interdisciplinary approach; multidisciplinary; patch clamp; receptor; receptor expression; receptor function; research study; response; somatosensory; tongue papilla

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 and texture of fat and how these mechanisms might contribute to dietary fat intake. Using obesity-prone and -resistant rat models we have previously identified differences in how the taste systems in these two strains 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 proposal describes two main specific aims that seek to identify and characterize fat receptive mechanisms that underlie the taste and texture of fat and investigate how these chemosensory pathways are modulated by dietary experience and the pathophysiological state of obesity. Specifically, we will use an approach including a multidisciplinary approach to test the following hypotheses: 1. Taste receptor cells and trigeminal neurons share common transduction pathways for the chemoreception of fatty acids (e.g. fat). We will test this by using molecular and immunocytochemical approaches to identify putative fat receptors including fatty acid sensitive K channels, the fatty acid transporter CD36 and several G protein-coupled receptors we have identified in taste cells and trigeminal neurons. Cell-based assays (imaging, electrophysiology) will characterize these "fat receptors" functionally. 2. Fat receptor expression in taste cells and trigeminal neurons is altered during high fat feeding in a manner that results in a decreased responsiveness to fatty acids. Based upon our preliminary data showing a reduction in responsiveness to fatty acids after the development of obesity on a high fat diet, we will use our multidisciplinary approach from genes through behavior to measure changes in expression and function of fat receptors as a function of macronutrient content of the diet.

随着西方饮食的传播，全球肥胖的发生率继续升级 心血管疾病，糖尿病，末期肾脏疾病和其他 与肥胖有关的疾病。在肥胖的所有原因中，主要的肥胖症似乎是选择 - 选择 多吃，运动少。与肥胖相关的选择之一是选择 高脂肪，热量致密的饮食。尽管对脂肪摄入与肥胖之间的联系进行了大量研究，但相对 关于脂肪的口味和质地的化学感应机制以及这些如何了解 机制可能会导致饮食脂肪摄入。使用容易肥胖和抗性的大鼠模型我们拥有 先前确定的在这两种菌株中的味觉系统对脂肪酸的反应方式的差异，这是一种提示 饮食脂肪，以及与基因表达和受体功能的差异如何相关。而且，我们 已经证明了这些化学感应机制是由饮食调节的 肥胖。该提案描述了旨在识别和表征脂肪接受的两个主要特定目的 脂肪的口味和质地的机制并研究了这些化学感应途径的方式 由饮食经验和肥胖的病理生理状态调节。具体来说，我们将使用 方法包括多学科方法来检验以下假设： 1。味觉受体细胞和三叉神经元具有共同的转导途径 脂肪酸（例如脂肪）。我们将使用分子和免疫细胞化学方法来识别这一点 推定的脂肪受体，包括脂肪酸敏感的K通道，脂肪酸转运蛋白CD36和几个G 我们在味道细胞和三叉神经元中鉴定的蛋白偶联受体。基于细胞的测定（成像， 电生理学）将在功能上表征这些“脂肪受体”。 2。在高脂进食期间，味觉细胞和三叉神经元中的脂肪受体表达以某种方式改变 这导致对脂肪酸的反应性降低。根据我们的初步数据显示减少 在高脂肪饮食上肥胖后对脂肪酸的反应性时，我们将使用我们的 从基因到行为的多学科方法，衡量脂肪表达和功能的变化 受体是饮食中大量营养素含量的函数。