Data_Sheet_1_Aerobic Exercise Improves Pulmonary Fibrosis by Improving Insulin Resistance and Inflammation in Obese Mice.docx

BackgroundPrevious studies have demonstrated that obesity is associated with pulmonary fibrosis. We attempted to identify whether regular aerobic exercise (AE) can protect against high-fat diet (HFD)-associated pulmonary fibrosis.MethodsForty-eight C57BL/6 mice were randomly assigned to four groups: chow group (Ch), chow plus exercise group (CE), obesity group (Ob), and obesity plus exercise group (OE). The mice were fed either an HFD or a chow diet for 16 weeks, and low-intensity aerobic exercise (AE) was performed in the last 8 weeks. We measured the degree of pulmonary fibrosis; pulmonary inflammation; oxidative stress parameters; insulin resistance-related indicators; the number of inflammatory cells in bronchoalveolar lavage fluid (BALF); the mRNA expression levels of IL-10, IL-1β, TGF-β, TNF-α, CXCL-1, IL-17, MMP-9, MPO, NE, and sirt-1; and the BALF levels of CXCL-1, IL-17, TGF-β, IL-10, IL-1β, and TNF-α in lung tissue.ResultsAE in obese mice protected against obesity-associated pulmonary fibrosis, chronic inflammation, pro-oxidative/antioxidative imbalance, and insulin resistance. AE ameliorated the HFD-induced inflammatory response and neutrophil infiltration in the lung. AE downregulated BALF levels of CXCL-1, IL-1β, TNF-α IL-17, and TGF-β but upregulated BALF levels of IL-10. AE decreased IL-1β, TGF-β, TNF-α, CXCL-1, IL-17, MMP-9, MPO, and NE mRNA expression levels but upregulated IL-10 and sirt-1 mRNA expression levels in the lung.ConclusionsAE protects against HFD-induced pulmonary fibrosis by improving obesity-associated insulin resistance, chronic low-grade inflammation, and pro-oxidative/antioxidative imbalance. AE improved HFD-induced pulmonary fibrosis by suppressing IL-17, TGF-β, NE, and MMP-9 expression and activating IL-10 and sirt-1 expression.

背景：既往研究表明，肥胖与肺纤维化之间存在关联。本研究旨在探究规律的有氧运动（AE）是否能够抵御高脂饮食（HFD）引起的肺纤维化。方法：将48只C57BL/6小鼠随机分为四组：普通饮食组（Ch）、普通饮食加运动组（CE）、肥胖组（Ob）和肥胖加运动组（OE）。小鼠在16周内分别接受高脂饮食或普通饮食，并在最后8周进行低强度有氧运动（AE）。本研究测量了肺纤维化的程度、肺炎症、氧化应激参数、胰岛素抵抗相关指标、支气管肺泡灌洗液（BALF）中炎症细胞的数量；IL-10、IL-1β、TGF-β、TNF-α、CXCL-1、IL-17、MMP-9、MPO、NE和sirt-1的mRNA表达水平；以及肺组织中BALF中CXCL-1、IL-17、TGF-β、IL-10、IL-1β和TNF-α的水平。结果：有氧运动在肥胖小鼠中能够保护其免受肥胖相关肺纤维化、慢性炎症、促氧化/抗氧化失衡以及胰岛素抵抗的影响。有氧运动改善了高脂饮食引起的肺部炎症反应和中性粒细胞浸润。有氧运动降低了BALF中CXCL-1、IL-1β、TNF-α、IL-17和TGF-β的水平，但提高了IL-10的水平。有氧运动降低了肺部IL-1β、TGF-β、TNF-α、CXCL-1、IL-17、MMP-9、MPO和NE的mRNA表达水平，但提高了IL-10和sirt-1的mRNA表达水平。结论：有氧运动通过改善肥胖相关的胰岛素抵抗、慢性低度炎症和促氧化/抗氧化失衡，保护小鼠免受高脂饮食诱导的肺纤维化。有氧运动通过抑制IL-17、TGF-β、NE和MMP-9的表达，并激活IL-10和sirt-1的表达，改善了高脂饮食诱导的肺纤维化。