Electrophysiological Analysis of Leptin Action

瘦素作用的电生理分析

• 批准号: 6622348
• 负责人: AARON G ROSEBERRY
• 金额: $ 4.64万
• 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 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6622348
• 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 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.老鼠 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 支出。 However, the exact mechanisms underlying the effects of leptin are 不太了解。 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.