母体不良营养状态能显著增加子代成年期发生糖尿病的风险，然而目前关于母代早期干预对子代糖代谢的影响及机制研究甚少。本研究前期工作表明：母鼠孕期高脂饮食能够导致子代出现糖代谢紊乱；母代运动干预能够有效改善子代成年期糖代谢异常；进一步发现miR-143可能通过靶向作用于成纤维细胞生长因子21（FGF21）起重要调控作用，但其中具体的机制尚不明确。本研究拟在此基础上开展母代早期干预及机制研究，通过建立跨代运动小鼠模型观察母鼠妊娠前期和妊娠期自主跑轮运动对子代糖代谢的保护效应；利用双荧光素酶系统明确miR-143与FGF21特异性结合；结合体外及体内实验，通过沉默或过表达miR-143，探讨miR-143/FGF21对子鼠糖耐量及糖异生的影响及调控机制，阐明miR-143/FGF21在母代运动改善子代糖代谢跨代效应中的作用。从全新的视角开展母代早期干预及机制研究，为糖尿病早期干预和预防提供理论依据。

Maternal poor nutrition can significantly increase the risks of developing diabetes in adult offspring. However, researches about the influences and mechanisms of maternal early intervention on glucose metabolism in offspring are limited. Our preliminary work showed that maternal high-fat diet during pregnancy could result in abnormal glucose metabolism in offspring mice. Maternal exercise intervention could effectively ameliorate glucose disorders in offspring. Further studies indicated that miR-143 potentially played an important role in this process by targeting to fibroblast growth factor 21 (FGF21). Based on these findings, our present study aimed to observe the protective effects of maternal voluntary wheel running before and during pregnancy on glucose metabolism in offspring. Subsequently, we will further investigate the effects of miR-143/FGF21 on glucose tolerance and gluconeogenesis potency in offspring mice by silencing or overexpression of miR-143 in vitro and in vivo, respectively. We further aimed to elucidate the underlying mechanisms of miR-143/FGF21 in glucose metabolism in offspring exposed to maternal exercise. From a novel perspective, we will carry out the maternal early intervention studies, and it is expected to provide an important theoretical basis for the early intervention and prevention of diabetes.