Role for Interleukin 10 in High-Fat Diet-Induced Inflammatory Atrial Remodeling and Fibrillation

Abstract

Background : Obesity, characterized by systemic low-grade inflammation, is considered a well-known risk for atrial fibrillation. In fact, interleukin 10（IL-10）, which is a potent anti-inflammatory cytokine, has been reported to decrease in obese and diabetic patients. We tested the hypothesis that genetic deletion of IL-10 exacerbates high-fat diet（HFD）–induced obesity-caused atrial inflammation, lipidosis, fibrosis, and fibrillation and that IL-10 therapy inhibits this pathology. Methods : Eight- to 10-week-old male CL57/B6（wild-type）mice and IL-10 knockout mice were divided into a 12-week HFD group and a 12-week normal-fat diet（NFD）group, respectively. The effect of IL-10 administration was also investigated. Results : HFD-induced obesity for 12 weeks significantly depressed serum levels of IL-10 but were found to increase several proinflammatory cytokines in wild-type mice. Adverse atrial remodeling, including atrial inflammation, lipidosis, and fibrosis, was induced in both wild-type and IL-10 knockout mice by HFD. Vulnerability to atrial fibrillation was also significantly increased by HFD. The total amount of epicardial adipose tissue＋pericardial adipose tissue volume was increased by HFD. Proinflammatory and profibrotic cytokines of epicardial adipose tissue＋pericardial adipose tissue were also upregulated. In contrast, the protein level of adiponectin was downregulated by HFD. These HFD-induced obesity-caused adverse effects were further exaggerated in IL-10 knockout mice in comparison to wild-type mice. Systemic IL-10 administration markedly ameliorated HFD-induced obesity-caused left atrial remodeling and vulnerability to atrial fibrillation, in addition to improving the quality of epicardial adipose tissue＋pericardial adipose tissue. Conclusions : Our results highlight IL-10 treatment as a potential therapeutic approach to limit the progression of HFD-induced obesity-caused atrial fibrillation.