Electrophysiological Analysis of Leptin Action

描述：（由申请人提供）肥胖是一个严重的健康问题， 据报道，近四分之一的美国和西方社会 美国人肥胖。瘦素是一种由脂肪组织分泌的蛋白质， 与食物摄入和能量平衡的调节有关。小鼠 缺乏瘦素或功能性瘦素受体（ObR）的人严重肥胖， 其他生理缺陷，和瘦素管理的小鼠导致一个 通过减少食物摄入和增加能量减少脂肪组织 支出然而，瘦素作用的确切机制是 没有被很好地理解。在这里提出的实验中，我们将尝试 阐明瘦素对食物摄入的作用机制， 能量平衡ObR的酪氨酸磷酸化在 调节瘦素的作用将通过建立 表达突变体ObRs的转基因小鼠，其中细胞内酪氨酸 已经变异了此外，还观察了瘦素对细胞外基质活性的影响。 将测量特定的神经元群体。含有特定 用GFP标记的神经元亚型将被创建，并且膜片钳技术 将用于测量瘦素对神经元活性的影响。 这些实验将大大加深我们对 瘦素，并可能提供新的途径干预到预防和 治疗肥胖症。

DESCRIPTION: (Provided By Applicant) Obesity is a serious health problem in the US and Western societies, and it has been reported that nearly one out of four Americans is obese. Leptin is a protein secreted by adipose tissue that has been implicated in the regulation of food intake and energy homeostasis. Mice lacking leptin or a functional leptin receptor (ObR) are grossly obese and show other physiological defects, and leptin administration to mice leads to a decrease in adipose tissue through reduced food intake and increased energy expenditure. However, the exact mechanisms underlying the effects of leptin are not well understood. In the experiments proposed here, we will attempt to elucidate the mechanisms by which leptin exerts its effects on food intake and energy homeostasis. The role that tyrosine phosphorylation of the ObR plays in mediating the effects of leptin will be examined through the creation of transgenic mice expressing mutant ObRs in which the intracellular tyrosines have been mutated. In addition, the effects of leptin on the activity of specific neuronal populations will be measured. Mice containing specific neuronal subtypes labeled with GFP will be created, and patch-clamp technology will be utilized to measure the effects of leptin on activity of the neurons. These experiments should greatly further our understanding of the effects of leptin, and may provide new avenues for intervention into the prevention and treatment of obesity.