生命早期的糖代谢紊乱可增加代谢综合征的风险，但原因和机制尚不清楚。我们前期的原创性研究发现，一种在孕期出现的血管紧张素II-1型受体自身抗体（AT1-AA）可使其子代生命早期肝糖原的含量呈现先升高后降低的现象，提示AT1-AA与生命早期糖代谢紊乱相关。本研究将利用小动物活体成像等技术，证实孕鼠体内的AT1-AA通过动态调节其子代肝脏葡萄糖转运体1（GLUT1）的膜转运能力，引起子代肝糖原由孕晚期的升高转为断乳期的降低；利用质粒过表达/RNA干扰等技术，证实蛋白糖基转移酶STT3A/3B表达的变化引起了GLUT1的糖基化修饰异常，这是导致GLUT1膜转运能力改变的关键因素。本研究拟证实“AT1-AA通过动态影响GLUT1的N-连接糖基化修饰作用，进而改变了GLUT1的膜转运能力，最终参与了生命早期的肝糖原代谢紊乱过程”，该研究为早期干预AT1-AA引起的代谢综合征提供新的潜在治疗靶点。

Early life disorders of glucose metabolism can increase the risk of metabolic syndrome, but the reasons and mechanisms are unclear. Our previous study found that AT1-AA, an autoantibody against angiotensin II-1 receptor that appeared during pregnancy, increased the progenitor glycogen of the offspring first and then decreased, suggesting that AT1-AA is associated with early life sugar metabolic disorders. In this study, we will use the live animal imaging technology to confirm that the AT1-AA can dynamically regulate the translocation of hepatic glucose transporter 1 (GLUT1), resulting in the fetal hepatic glycogen in the third trimester of pregnancy increase first and then decrease in the weaning period. Plasmid transfection /RNA interference technology will be used to identify that the glycosylation abnormality is the key reason of the change of GLUT1 membrane translocation. This study will confirm that "AT1-AA participate in early glycogen disordering process by affecting N-linked glycosylation of GLUT1 and then regulating membrane translocation of GLUT1", which will provide a potential target of AT1-AA-induced metabolism Syndrome.