巨大儿是导致儿童至青春期肥胖及成年期代谢综合症的重要危险因素。脂肪因子在肥胖和代谢综合症中起重要作用。前期研究发现不同体重新生儿脐血中特定脂肪因子(CCDC80)的表达水平不同，但其在巨大儿中表达效果和作用机制尚不清楚。本项目的研究目标是1）通过CCDC80基因敲除的动物模型对高脂膳食诱导造成孕鼠肥胖，观察比较CCDC80对仔鼠生长发育和营养代谢的影响，明确CCDC80表达水平对肥胖和胰岛素抵抗发展的生理功能；2）在已建立的人群孕期队列的基础上，研究孕妇营养状况、炎症因子和胰岛素抵抗状态以及胎儿CCDC80基因多态性对胎儿CCDC80表达水平的影响，从人群角度明确CCDC80表达的差异性对巨大儿发生的影响。3）通过体外质粒转化细胞实验，分析CCDC80调控区多态性与其表达的相关性。从分子、模型动物和群体分析的不同层次研究CCDC80的调控机制，为深入研究其对胎儿生长发育影响提供基础数据。

Macrosomia is a major risk factor leading to childhood and adolescent obesity and adult metabolic syndrome. Adipokines play an important role in obesity and metabolic syndrome. Our preliminary studies found that the expression level of a novel adipokine (CCDC80) in umbilical cord blood is associated with birth weight of neonates, but the underlying mechanism is unclear. There are three main research goals for this project. The first is to build a CCDC80 knockout mouse model of high fat diet induced obesity to investigate the role of CCDC80 in the growth and nutrient metabolism of mouse offspring. The second is to investigate the roles of maternal nutritional status and insulin resistance and maternal/neonates CCDC80 promoter polymorphism in regulation of neonatal CCDC80 expression, based on population study using our existing collection of pregnant mothers and neonates. The third is to perform in vitro transfection study to analyze ccdc80 promoter activity and the regulation of its expression by polymorphic change of CCDC80 promoter sequence. This project is intended to provide further understanding of the mechanism of fetal growth and development.