Department of Cardiovascular Disease, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
Department of Sport Science, Korea Institute of Sport Science, Seoul, Republic of Korea.
BMC Med. 2022 Nov 8;20(1):429. doi: 10.1186/s12916-022-02629-1.
Non-alcoholic fatty liver disease (NAFLD) can lead to pulmonary dysfunction that is associated with pulmonary inflammation. Moreover, little is known regarding the therapeutic role of exercise training on pulmonary pathophysiology in NAFLD. The present study aimed to investigate the effect of exercise training on high-fat high-carbohydrate (HFHC)-induced pulmonary dysfunction in C57BL/6 mice.
Male C57BL/6 mice (N = 40) were fed a standard Chow (n = 20) or an HFHC (n = 20) diet for 15 weeks. After 8 weeks of dietary treatment, they were further assigned to 4 subgroups for the remaining 7 weeks: Chow (n = 10), Chow plus exercise (Chow+EX, n = 10), HFHC (n = 10), or HFHC plus exercise (HFHC+EX, n = 10). Both Chow+EX and HFHC+EX mice were subjected to treadmill running.
Chronic exposure to the HFHC diet resulted in obesity with hepatic steatosis, impaired glucose tolerance, and elevated liver enzymes. The HFHC significantly increased fibrotic area (p < 0.001), increased the mRNA expression of TNF-α (4.1-fold, p < 0.001), IL-1β (5.0-fold, p < 0.001), col1a1 (8.1-fold, p < 0.001), and Timp1 (6.0-fold, p < 0.001) in the lung tissue. In addition, the HFHC significantly altered mitochondrial function (p < 0.05) along with decreased Mfn1 protein levels (1.8-fold, p < 0.01) and increased Fis1 protein levels (1.9-fold, p < 0.001). However, aerobic exercise training significantly attenuated these pathophysiologies in the lungs in terms of ameliorating inflammatory and fibrogenic effects by enhancing mitochondrial function in lung tissue (p < 0.001).
The current findings suggest that exercise training has a beneficial effect against pulmonary abnormalities in HFHC-induced NAFLD through improved mitochondrial function.
非酒精性脂肪性肝病（NAFLD）可导致与肺部炎症相关的肺功能障碍。此外，关于运动训练对 NAFLD 肺病理生理学的治疗作用知之甚少。本研究旨在探讨运动训练对 C57BL/6 小鼠高脂高碳水化合物（HFHC）诱导的肺功能障碍的影响。
雄性 C57BL/6 小鼠（N = 40）喂食标准饲料（n = 20）或 HFHC 饮食（n = 20）15 周。经过 8 周的饮食治疗，他们进一步分为以下 4 个亚组，进行接下来的 7 周：标准饲料组（Chow，n = 10）、标准饲料+运动组（Chow+EX，n = 10）、HFHC 饮食组（HFHC，n = 10）或 HFHC 饮食+运动组（HFHC+EX，n = 10）。Chow+EX 和 HFHC+EX 组的小鼠都进行了跑步机跑步。
慢性暴露于 HFHC 饮食导致肥胖、肝脂肪变性、葡萄糖耐量受损和肝酶升高。HFHC 显著增加了纤维化面积（p < 0.001），增加了 TNF-α（4.1 倍，p < 0.001）、IL-1β（5.0 倍，p < 0.001）、col1a1（8.1 倍，p < 0.001）和 TIMP1（6.0 倍，p < 0.001）在肺组织中的表达。此外，HFHC 还显著改变了线粒体功能（p < 0.05），同时降低了 Mfn1 蛋白水平（1.8 倍，p < 0.01）和增加了 Fis1 蛋白水平（1.9 倍，p < 0.001）。然而，有氧运动训练通过改善肺组织中的线粒体功能，显著减轻了肺部的这些病理生理变化，从而改善了炎症和纤维化效应（p < 0.001）。
目前的研究结果表明，运动训练通过改善线粒体功能对 HFHC 诱导的 NAFLD 中的肺部异常具有有益作用。
