Hyperleptinemia Exacerbates High‐Fat Diet‐Mediated Atrial Fibrosis and Fibrillation
Obesity, including metabolic syndrome (Mets), is a well‐known independent risk factor of AF.3 Recently, it was reported that high‐fat diet (HFD) induced left atrial (LA) fibrosis and AF in a sheep model.6 Meanwhile, LA low voltage area that represents atrial fibrotic tissue7 was frequently observed in Mets subjects during AF ablation.8 These experimental and clinical observations suggests that atrial fibrosis is one of the underlying mechanisms of obesity‐related AF. However, little is known about the molecular pathways responsible for these changes.
Leptin, a 16 kDa peptide hormone, which is mainly secreted by adipocytes, regulates appetite and body fat mass predominantly through the central nervous system.9 Leptin has also been identified as a proinflammatory adipocytokine that can provoke inflammatory‐mediated interstitial fibrosis in several peripheral organs.11 In addition, experimental and clinical evidence has revealed the relationship between leptin and cardiovascular disease, including AF.13 For example, Bobbert et al. reported that high leptin expression in patients with nonischemic dilated cardiomyopathy and inflammatory cardiomyopathy was associated with the progression of heart failure.15 We previously demonstrated that leptin signaling is essential for the pathogenesis of atrial fibrosis and AF induced by angiotensin II (AngII) in mice, and leptin‐deficient ob/ob (Ob) mice are resistant to AngII‐mediated inflammatory profibrotic changes.16 Although hyperleptinemia is usually observed in obese subjects, the direct relationship with atrial fibrosis and AF is remained to be studied.
Therefore, we tested the hypothesis that hyperleptinemia exacerbates HFD‐mediated atrial fibrosis and AF.