Gender Differences in Leptin Signaling

描述：(申请人提供)：肥胖是一个巨大的健康问题，几乎没有有效的治疗方法。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发生的 控制食物摄入量和能量消耗的中央机制。瘦素是 由脂肪细胞分泌，作为脂肪储存的外周信号 对大脑的影响。在体脂百分比上存在性别差异，在 身体脂肪的分布，我们已经确定了性别差异 对集中给药的瘦素敏感。目前的实验是 建议确定性腺激素，特别是雌激素，是否影响 瘦素关键信号变异体的表达及其敏感性 受体(Ob-Rb)。第一系列实验将调查是否有 原位杂交中Ob-Rb分布和表达的性别差异 杂交实时定量聚合酶链式反应和蛋白质印迹分析。在第二组 实验，我们将调查是否有不同的激活 作为瘦素受体信号一部分被激活的细胞内蛋白 利用Western Blot分析和核糖核酸酶分析CASCADE、STAT3和SOCS-3 保护化验说。最后，我们将评估性腺激素雌激素， 通过比较去性腺动物对Ob-Rb表达和激活的影响 无论有没有激素替代和测量Ob-Rb分布， 表达和激活。

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.