MECHANISMS OF PERIPHERAL FAT DETECTION

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、终末期肾病等疾病也相应增加 肥胖相关的疾病。在导致肥胖的所有原因中，最主要的原因似乎是选择--选择 多吃少运动。与肥胖有关的选择之一是选择一个 高脂肪、高热量的饮食。尽管对脂肪摄入和肥胖之间的联系进行了很多研究，但相对 对于脂肪的味道和质地背后的化学感觉机制以及这些机制如何，人们知之甚少。 这些机制可能有助于膳食脂肪的摄取。使用我们有肥胖倾向和抵抗力的大鼠模型 之前发现这两种菌株的味觉系统对脂肪酸的反应方式不同，这是一个线索 饮食脂肪，以及这与基因表达和受体功能的差异是如何关联的。此外，我们 已经证明了这些化学感觉机制是由饮食和 肥胖。该提案描述了寻求识别和表征脂肪接受性的两个主要具体目标 脂肪的味道和质地的机制，并研究这些化学感觉途径是如何 受饮食经验和肥胖的病理生理状态的影响。具体地说，我们将使用 方法包括多学科方法来检验以下假设： 1.味觉感受器细胞和三叉神经细胞共同的化学感受通路。 脂肪酸(如脂肪)。我们将通过使用分子和免疫细胞化学方法来验证这一点 可能的脂肪受体包括脂肪酸敏感的K通道、脂肪酸转运体CD36和几个G 我们已经在味觉细胞和三叉神经细胞中发现了蛋白质偶联受体。基于细胞的分析(成像， 电生理学)将从功能上描述这些“脂肪受体”。 2.在高脂饮食过程中，味觉细胞和三叉神经细胞的脂肪受体表达发生改变。 这会导致对脂肪酸的反应性降低。根据我们的初步数据显示 在高脂肪饮食引起肥胖后对脂肪酸的反应，我们将使用我们的 从基因到行为的多学科方法来衡量脂肪表达和功能的变化 受体作为饮食中常量营养素含量的函数。

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.