NOVEL HUMORAL FACTORS REGULATING LEPTIN EXPRESSION

描述 能量平衡是通过复杂的反馈回路来维持的 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 过多的健康风险与肥胖症有因果关系，包括糖尿病， 心血管疾病和某些癌症。瘦素表达是 在转录水平上动态调节， 脂肪组织水平和进食状态的总体变化。主 该提案的目的是鉴定和表征新的体液免疫， 调节小鼠肥胖（ob）基因表达的因子，编码 瘦素激素。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。本试验将用于 筛选小牛和胎牛血清提取物中的小有机 诱导或抑制 ob基因的表达。体液因子将被纯化， 以标准方法为特征。一旦确定，这些水平 将测量人、小鼠和大鼠血清中的因子， 一般营养和喂养状况。最后，将努力 确定这些因子的作用是否通过转录介导 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.