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.

既往研究业已证实，肥胖与肺纤维化密切相关。本研究旨在探讨规律的有氧运动（AE）是否能够抵御高脂饮食（HFD）引发的肺纤维化。研究方法：将48只C57BL/6小鼠随机分为四组：普通饲料组（Ch）、普通饲料加运动组（CE）、肥胖组（Ob）和肥胖加运动组（OE）。小鼠被喂养高脂或普通饲料16周，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程度、肺炎症程度、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。研究结果：AE能够保护肥胖小鼠免受肥胖相关肺纤维化、慢性炎症、促氧化/抗氧化失衡和胰岛素抵抗的影响。AE改善了高脂饮食引发的肺部炎症反应和粒细胞浸润。AE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。AE降低了肺组织中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。研究结论：AE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，抵御高脂饮食引发的肺纤维化。AE通过抑制IL-17、TGF-β、NE和MMP-9的表达，激活IL-10和sirt-1的表达，改善高脂饮食引发的肺纤维化。