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.
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 diabeticpatients. 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.
Authors: Kelsey H Collins; Kristin L Lenz; Eleanor N Pollitt; Daniel Ferguson; Irina Hutson; Luke E Springer; Arin K Oestreich; Ruhang Tang; Yun-Rak Choi; Gretchen A Meyer; Steven L Teitelbaum; Christine T N Pham; Charles A Harris; Farshid Guilak Journal: Proc Natl Acad Sci U S A Date: 2021-01-05 Impact factor: 11.205
Authors: Nicholas Stafford; Farryah Assrafally; Sukhpal Prehar; Min Zi; Ana M De Morais; Arfa Maqsood; Elizabeth J Cartwright; Werner Mueller; Delvac Oceandy Journal: Front Pharmacol Date: 2020-10-30 Impact factor: 5.810