Electrophysiological Analysis of Leptin Action

描述：(申请人提供)肥胖是老年人的严重健康问题 美国和西方社会，据报道，近四分之一的人 美国人很肥胖。瘦素是一种由脂肪组织分泌的蛋白质，具有 与食物摄取和能量平衡的调节有关。老鼠 缺乏瘦素或功能性瘦素受体(OBR)会严重肥胖，并表现为 其他生理缺陷，给小鼠服用瘦素会导致 通过减少食物摄入量和增加能量来减少脂肪组织 支出。然而，瘦素作用的确切机制是 不是很清楚。在这里提出的实验中，我们将尝试 阐明瘦素影响食物摄入量和 能量平衡。OBR酪氨酸磷酸化在细胞周期调控中的作用 瘦素的调节作用将通过产生 表达突变型OBRS的转基因小鼠，其中细胞内酪氨酸 都发生了突变。此外，瘦素对血管紧张素转换酶活性的影响 将对特定的神经元群体进行测量。小鼠含有特定的 将创建标记GFP的神经元亚型，并采用膜片钳技术 将被用来测量瘦素对神经元活动的影响。 这些实验应该会极大地加深我们对 瘦素，并可能提供新的途径，干预预防和 肥胖的治疗。

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.