糖尿病致心房纤维化是糖尿病患者发生房颤的主要原因，心外膜脂肪组织(EAT)依靠旁分泌炎性和脂肪细胞因子参与心房纤维化过程，而促进EAT中白色脂肪棕色化可能抑制糖尿病致心房纤维化进程。已证实PPARγ/FGF21通过活化FGFR1-β-Klotho复合体促进白色脂肪棕色化，而本课题组前期工作观察到高糖诱导的miR-21表达上调可抑制EAT棕色化过程，且其机制可能与负性调控FGFR1有关。本项目由此提出假设：高糖可能通过上调EAT中miR-21表达、负性调控FGFR1表达，从而抑制PPARγ/FGF21/FGFR1-β-Klotho信号轴活化，减弱EAT棕色化，加重心房纤维化的发生。本项目拟复制在体和离体糖尿病致心房纤维化模型，采用细胞共培养、基因敲除、电生理等实验方法，探讨miR-21调控EAT棕色化的分子机制及其在糖尿病致心房纤维化中的作用，进一步完善糖尿病致心房纤维化的分子机制。

Diabetes mellitus (DM) is one of the major risk factors for the occurrence of atrial fibrillation(AF) by acting on atrial fibrosis mechanisms. By releasing pro-inflammatory cytokines and adipokines, epicardial adipose tissue (EAT) contributes to the process of atrial fibrosis. And the browning of white adipose in EAT might mitigate the process of atrial fibrosis induced by DM. It has been proved that peroxisome proliferator-activated receptor γ (PPARγ)/fibroblast growth factor 21 (FGF21) signaling pathway facilitates the browning of white adipose through activating the complex of fibroblast growth factor receptor 1 (FGFR1)- β-Klotho. And the current research group observed that miR-21 expression induced by high glucose inhibited the browning of EAT, which might be associated with its negative regulating of FGFR1. Therefore, we put forward the hypothesis that high glucose activates miR-21 expression in EAT, negatively regulates the expression of FGFR1, then contributes to the inhibitory effect of PPARγ/FGF21/FGFR1-β-Klotho signaling pathway and browning of EAT, which results in the pathogenesis of atrial fibrosis. Through establishing DM-induced atrial fibrosis model in vitro and in vivo, and using experimental methods, such as cell co-culture, gene knockout and electrophysiological techniques, etc, we are going to evaluate the role of miR-21 in the process of the EAT browning and DM-induced atrial fibrosis. These findings will provide novel molecular mechanisms involved in DM-induced atrial fibrosis.