Gender Differences in Leptin Signaling

瘦素信号传导的性别差异

• 批准号: 6487344
• 负责人: Deborah J Clegg
• 金额: $ 4.42万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-01 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6487344
• 关键词: RNase protection assay; adipose tissue; biological signal transduction; estradiol; gender difference; hormone receptor; hormone regulation /control mechanism; hypothalamus; in situ hybridization; laboratory rat; leptin; polymerase chain reaction; receptor expression; receptor sensitivity; western blottings

DESCRIPTION: (provided by applicant): Obesity is a health problem of enormous proportions with few effective therapeutic treatments. The regulation of body weight and body adiposity occurs through coordinated actions of peripheral and central mechanisms, which control food intake and energy expenditure. Leptin is secreted from adipocytes and functions as a peripheral signal of lipid stores to the brain. There are gender difference in percent body fat as well as in the distribution of body fat, and we have determined there are gender differences in sensitivity to centrally administered leptin. The present experiments are proposed to determine if gonadal hormones, specifically estrogen, effects the expression and sensitivity of the critical signaling variant of the leptin receptor (Ob-Rb). The first series of experiments will investigate if there are gender differences in distribution and expression of the Ob-Rb using in situ hybridization real-time PCR and Western blot analysis. In the second set of experiments, we will investigate if there are differences in the activation of intracellular proteins activated as part of the leptin receptor-signaling cascade, STAT3 and SOCS-3, by utilizing Western Blot analysis and Ribonuclease Protection Assays. Lastly, we will assess whether the gonadal hormone estrogen, affects Ob-Rb expression and activation, by comparing gonadectomized animals with and without hormone replacement and measuring Ob-Rb distribution, expression, and activation.

描述：（由申请人提供）：肥胖是一个影响巨大的健康问题，但有效的治疗方法很少。身体的调节 体重和身体肥胖是通过外周和身体的协调作用而发生的 控制食物摄入和能量消耗的中央机制。瘦素是 由脂肪细胞分泌，作为脂质储存的外周信号发挥作用 到大脑。身体脂肪百分比以及体重方面存在性别差异 身体脂肪的分布，我们已经确定存在性别差异 对集中管理的瘦素的敏感性。目前的实验是 建议确定性腺激素，特别是雌激素是否会影响 瘦素关键信号变体的表达和敏感性 受体（Ob-Rb）。第一系列实验将调查是否存在 原位观察 Ob-Rb 分布和表达的性别差异 杂交实时PCR和蛋白质印迹分析。在第二组中 实验中，我们将研究激活是否存在差异 作为瘦素受体信号传导一部分的细胞内蛋白质被激活 利用蛋白质印迹分析和核糖核酸酶进行级联、STAT3 和 SOCS-3 保护测定。最后，我们将评估性腺激素雌激素是否 通过比较性腺切除动物来影响 Ob-Rb 表达和激活 有或没有激素替代并测量 Ob-Rb 分布， 表达和激活。