NOVEL HUMORAL FACTORS REGULATING LEPTIN EXPRESSION

描述 能量动态平衡通过复杂的反馈回路来维持 通过循环体液因子如胰岛素，胰高血糖素， 糖皮质激素和瘦素。这个系统的崩溃导致了一个 与肥胖相关的过多健康风险，包括糖尿病， 心血管疾病和某些类型的癌症。瘦素的表达是 在转录水平上动态调节以响应 脂肪组织水平和进食状态的总体变化。初级阶段 这项建议的目的是识别和表征新的幽默 调节小鼠肥胖(Ob)基因表达的因子，编码 对于荷尔蒙瘦素。一个高度敏感和生物健全的细胞- 将开发一种检测ob表达的方法。 利用荧光素酶作为报告基因。这项化验将被用于 小牛和胎牛血清小分子有机提取物的筛选 诱导或抑制的化合物和新型多肽激素 Ob基因的表达。体液因素将被提纯并 以标准方法为特点的。一旦确定，这些物质的水平 人、小鼠和大鼠血清中的因子将作为以下函数进行测量 一般营养和摄食状态。最后，我们将努力 确定这些因子的作用是否通过转录调节 已知调节瘦素表达的因子。

DESCRIPTION Energy homeostasis is maintained through complex feedback loops integrated via circulating humoral factors such as insulin, glucagon, glucocorticoids and leptin. The breakdown of this system results in a plethora of health risks causally related to obesity including diabetes, cardiovascular disease and certain types of cancer. Leptin expression is dynamically regulated at the level of transcription in response to overall changes in adipose tissue levels and feeding state. The primary objective of this proposal is to identify and characterize novel humoral factors that regulate expression of the mouse obese (ob) gene, encoding for the hormone leptin. A highly sensitive and biologically sound cell- based assay will e developed for the detection of ob expression utilizing luciferase as a reporter gene. This assay will be used to screen extracts of calf and fetal bovine serum for small organic compounds and novel polypeptide hormones that induce or repress expression of the ob gene. Humoral factors will be purified and characterized by standard methods. Once identified, the levels of these factors in human, mouse, and rat serum will be measured as a function of general nutrition and feeding state. Finally, an effort will be made to determine if the effects of these factors are mediated via transcription factors known to regulate leptin expression.