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，全球肥胖症的发病率继续上升， 心血管疾病、糖尿病、终末期肾病和其他 肥胖相关的疾病在所有肥胖的原因中，最主要的一个似乎是选择-选择 多吃少运动。与肥胖有关的选择之一是选择 高脂肪高热量饮食尽管有很多关于脂肪摄入和肥胖之间联系的研究， 人们对脂肪味道和质地背后的化学感受机制以及这些机制如何作用知之甚少 机制可能有助于膳食脂肪摄入。使用肥胖倾向和抵抗的大鼠模型， 先前确定的差异，在如何味觉系统在这两个菌株的脂肪酸，一个线索， 膳食脂肪，以及这与基因表达和受体功能差异的相关性。而且我们 已经证明，这些化学感受机制是由饮食和发育调节的， 肥胖该提案描述了两个主要的具体目标，旨在确定和表征脂肪接受 脂肪的味道和质地的基础机制，并研究这些化学感受途径是如何 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，以测试以下假设： 1.味觉感受器细胞和三叉神经元共享共同的化学感受传导途径， 脂肪酸（例如脂肪）。我们将通过分子和免疫细胞化学方法来检测这一点， 假定的脂肪受体包括脂肪酸敏感性K通道、脂肪酸转运蛋白CD 36和几种G 我们已经在味觉细胞和三叉神经元中鉴定了蛋白偶联受体。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.在高脂喂养过程中，味觉细胞和三叉神经元中脂肪受体的表达发生了变化， 导致对脂肪酸的反应性降低。根据我们的初步数据显示 在高脂肪饮食导致肥胖后，我们将使用我们的 从基因到行为的多学科方法来测量脂肪表达和功能的变化 受体作为饮食的常量营养素含量的函数。