宫内生长受限（IUGR）个体成年后代谢综合征的发病率明显增加，其机制在于宫内发育不良造成机体胰岛素抵抗和胰腺发育受损。课题组前期在国家自然基金资助下发现外周组织和下丘脑中胰岛素PI3K信号通路异常。转录因子FoxA2是PI3K信号通路下游的关键基因，它通过下丘脑神经元调节摄食和代谢率以及调控胰腺分化发育和胰岛素分泌共同调控机体血糖稳态。本课题在前期研究基础上，通过体内体外实验系统研究IUGR子代发育成长过程中，下丘脑中FoxA2和靶基因的表观遗传学改变及所引起的神经元电生理学变化对摄食和代谢率影响；以及胰腺中FoxA2和靶基因的表观遗传学改变及所引起的电生理学变化对β细胞发育和分泌功能的影响；探讨FoxA2过表达的干预作用。研究结果有助于深入理解IUGR与代谢综合征的分子联系，为进一步认识胎儿起源的成人疾病，预防和减少代谢综合征的发生提供理论依据和实验基础。

Intrauterine growth restriction (IUGR) leads to the development of adulthood metabolic syndrome, which originated from organism insulin resistance and impaired development of the pancreas caused by poor intrauterine growth. The results of our preliminary research funded by the National Natural Science Foundation, indicated that insulin-PI3K signaling pathway was disturbed in the peripheral tissue and hypothalamus of IUGR offspring. Transcription factor FoxA2, the key downstream gene of PI3K pathway, maintains the glucose hemeostasis by regulating feeding behavior and metabolsm in the neurons of the hypothalamus and by promoting differentiation,development and insulin secretion of the pancreas. Based on previous studies, this project will investigate the epigenetic changes in the FoxA2 and target genes and subsequently the electrophysiological changes in the neurons of the hypothalamus, then analyze the effect on feeding behavior and energy expenditure. Meanwhile, this study will explore the epigenetic changes in the FoxA2 and target genes and subsequently the electrophysiological changes in the β cell, then analyze the impact on development and secretory function of islet. Further study will focus on the intervention effect of FoxA2 overexpression. The study above will elucidate the pathogenesis of fetal origins of adult metabolic syndrome, provide the basis of theory and experiment for knowing fetal origins of adult disease further, and for preventing and reducing the occurrence of metabolic syndrome.