Electrophysiological Analysis of Leptin Action

瘦素作用的电生理分析

• 批准号: 6710030
• 负责人: Aaron G Roseberry
• 金额: $ 0.64万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6710030
• 关键词: adipose tissue; artificial chromosomes; bioenergetics; biological signal transduction; electrophysiology; gene expression; gene mutation; genetic regulatory element; genetically modified animals; green fluorescent proteins; homeostasis; hormone receptor; hormone regulation /control mechanism; hypothalamus; laboratory mouse; leptin; neurons; neuropeptide Y; nutrient intake activity; nutrition related tag; obesity; phenylalanine; phosphorylation; proopiomelanocortin; tyrosine; voltage /patch clamp

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.

描述：（由申请人提供）肥胖是一个严重的健康问题 美国和西方社会，据报道，四分之一 美国人肥胖。瘦素是一种由脂肪组织分泌的蛋白质 与食物摄入和能量稳态的调节有关。老鼠 缺乏瘦素或功能性瘦素受体（OBR）非常肥胖，并显示 其他生理缺陷和对小鼠的瘦素给药导致 通过减少食物摄入和增加能量来减少脂肪组织 支出。但是，瘦素作用的确切机制是 不太了解。在这里提出的实验中，我们将尝试 阐明瘦素对食物摄入的影响和 能量稳态。 OBR酪氨酸磷酸化的作用在 介导瘦素的作用将通过创建来检查 表达突变体的转基因小鼠，其中细胞内酪氨酸 已经突变了。另外，瘦素对 将测量特定的神经元种群。包含特定的小鼠 将创建标记为GFP的神经元亚型，并进行补丁钳技术 将用于测量瘦素对神经元活性的影响。 这些实验应大大进一步我们对 瘦素，并可能提供新的途径，以干预预防和 肥胖的治疗。