Atrial fibrillation (AF) is the most common cardiac arrhythmia nowadays. The occurrence of AF is closely associated with obesity. Cadherin‐11 (Cad‐11), as a member of the cadherin family, can make a contribution to diet‐induced obesity and it will be informative to know whether Cad‐11 exerts its effects on atrial remodeling and AF vulnerability in a diet‐induced obesity model. In this study, we demonstrated that the expression of Cad‐11 was significantly upregulated in the left atrium of AF patients with obesity and mice following 16 weeks of high‐fat diet (HFD) feeding. Further confirmed that Cad‐11 could regulate the activity of atrial fibroblasts by participating in inducing proinflammatory cytokines production. At animal levels, we found that although there was a lack of statistical difference in body weight, Cad‐11^−/− mice could markedly improve impaired glucose tolerance and hyperlipidemia. Adverse atrial structural remodeling, including atrial enlargement, inflammation, and fibrosis provoked by HFD feeding were mitigated in Cad‐11^−/− mice. Mechanistically, Cad‐11 activated mitogen‐activated protein kinases and nuclear factor‐κB for interleukin‐6 production in atrial fibroblasts that may contribute to the atrial fibrosis process in obesity‐related AF, suggesting Cad‐11 might be a new therapeutic target for obesity‐related AF.

中文翻译：

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Cadherin-11 缺乏可减轻高脂肪饮食引起的炎症性心房重构和心房颤动的易感性

心房颤动（AF）是当今最常见的心律失常。AF的发生与肥胖密切相关。Cadherin-11 (Cad-11) 作为钙粘蛋白家族的一员，可以对饮食引起的肥胖做出贡献，了解 Cad-11 是否对饮食中的心房重塑和 AF 易感性产生影响将是有益的。诱导肥胖模型。在这项研究中，我们证明了在高脂饮食 (HFD) 喂养 16 周后，肥胖 AF 患者和小鼠左心房中 Cad-11 的表达显着上调。进一步证实 Cad-11 可以通过参与诱导促炎细胞因子的产生来调节心房成纤维细胞的活性。在动物水平上，我们发现虽然体重没有统计学差异，但 Cad-11 ^-/-小鼠可显着改善糖耐量减低和高脂血症。在 Cad-11 ^-/-小鼠中，HFD 喂养引起的不良心房结构重塑，包括心房扩大、炎症和纤维化得到缓解。从机制上讲，Cad-11 激活丝裂原活化蛋白激酶和核因子-κB 用于心房成纤维细胞中白细胞介素-6 的产生，这可能有助于肥胖相关 AF 的心房纤维化过程，表明 Cad-11 可能是肥胖症的新治疗靶点相关的 AF。