학술논문
Interleukin 10 Treatment Ameliorates High-Fat Diet–Induced Inflammatory Atrial Remodeling and Fibrillation
Document Type
Academic Journal
Author
Kondo, Hidekazu; Abe, Ichitaro; Gotoh, Koro; Fukui, Akira; Takanari, Hiroki; Ishii, Yumi; Ikebe, Yuki; Kira, Shintaro; Oniki, Takahiro; Saito, Shotaro; Aoki, Kohei; Tanino, Tomomi; Mitarai, Kazuki; Kawano, Kyoko; Miyoshi, Miho; Fujinami, Mami; Yoshimura, Seiichiro; Ayabe, Reika; Okada, Norihiro; Nagano, Yasuko; Akioka, Hidefumi; Shinohara, Tetsuji; Akiyoshi, Kumiko; Masaki, Takayuki; Teshima, Yasushi; Yufu, Kunio; Nakagawa, Mikiko; Takahashi, Naohiko
Source
Circulation: Arrhythmia and Electrophysiology. May 01, 2018 11(5):e006040-e006040
Subject
Language
English
ISSN
1941-3149
Abstract
BACKGROUND:: Obesity, characterized by systemic low-grade inflammation, is considered a well-known risk for atrial fibrillation. In fact, IL-10 (interleukin 10), which is a potent anti-inflammatory cytokine, has been reported to decrease in obese and diabetic patients. We tested the hypotheses forwarding 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. In addition, 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 enhanced by HFD. With regard to epicardial and pericardial adipose tissue, the total amount of epicardial adipose tissue+pericardial adipose tissue volume was increased by HFD. Besides, 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.