Interleukin 10 Treatment Ameliorates High-Fat Diet–Induced Inflammatory Atrial Remodeling and Fibrillation

• DOI: 10.1161/circep.117.006040
• Publication Date: 2018-05-10T09:15:10Z
• Authors: Hidekazu Kondo; Ichitaro Abe; Koro Gotoh; Akira Fukui; Hiroki Takanari; Yumi Ishii; Yuki Ikebe; Shintaro Kira; Takahiro Oniki; Shotaro Saito; Kohei Aoki; Tomomi Tanino; Kazuki Mitarai; Kyoko Kawano; Miho Miyoshi; Mami Fujinami; Seiichiro Yoshimura; Reika Ayabe; Norihiro Okada; Yasuko Nagano; Hidefumi Akioka; Tetsuji Shinohara; Kumiko Akiyoshi; Takayuki Masaki; Yasushi Teshima; Kunio Yufu; Mikiko Nakagawa; Naohiko Takahashi
• Keywords: Inflammation; Male; Mice, Knockout; 2. Zero hunger; Anti-Inflammatory Agents; Action Potentials; Atrial Remodeling; Diet, High-Fat; Lipid Metabolism; Fibrosis; Interleukin-10; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; 03 medical and health sciences; 0302 clinical medicine; Adipose Tissue; Heart Rate; Atrial Fibrillation; Animals; Heart Atria; Anti-Arrhythmia Agents

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.