Key Laboratory of Exercise and Health Sciences of Ministry of Education, School of Kinesiology, Shanghai University of Sport, Shanghai, China.
Department of Physiology, Second Military Medical University, Shanghai, China.
J Appl Physiol (1985). 2017 Oct 1;123(4):717-727. doi: 10.1152/japplphysiol.00652.2016. Epub 2017 Jun 29.
Exercise training is advocated for treating chronic inflammation and obesity-related metabolic syndromes. Glucocorticoids (GCs), the anti-inflammatory hormones, are synthesized or metabolized in extra-adrenal organs. This study aims to examine whether exercise training affects obesity-associated pulmonary inflammation by regulating local GC synthesis or metabolism. We found that sedentary obese () mice exhibited increased levels of interleukin (IL)-1β, IL-18, monocyte chemotactic protein (MCP)-1, and leukocyte infiltration in lung tissues compared with lean mice, which was alleviated by 6 wk of exercise training. Pulmonary corticosterone levels were decreased in mice. Exercise training increased pulmonary corticosterone levels in both lean and mice. Pulmonary corticosterone levels were negatively correlated with IL-1β, IL-18, and MCP-1. Immunohistochemical staining of the adult mouse lung sections revealed positive immunoreactivities for the steroidogenic acute regulatory protein, the cholesterol side-chain cleavage enzyme (CYP11A1), the steroid 21-hydroxylase (CYP21), 3β-hydroxysteroid dehydrogenase (3β-HSD), and type 1 and type 2 11β-hydroxysteroid dehydrogenase (11β-HSD) but not for 11β-hydroxylase (CYP11B1). Exercise training significantly increased pulmonary 11β-HSD1 expression in both lean and mice. In contrast, exercise training per se had no effect on pulmonary 11β-HSD2 expression, although pulmonary 11β-HSD2 levels in mice were significantly higher than in lean mice. RU486, a glucocorticoid receptor antagonist, blocked the anti-inflammatory effects of exercise training in lung tissues of obese mice and increased inflammatory cytokines in lean exercised mice. These findings indicate that exercise training increases pulmonary expression of 11β-HSD1, thus contributing to local GC activation and suppression of pulmonary inflammation in obese mice. Treadmill training leads to a significant increase in pulmonary corticosterone levels in mice, which is in parallel with the favorable effects of exercise on obesity-associated pulmonary inflammation. Exercise training increases pulmonary 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression but has no significant effect on 11β-HSD2 expression in both lean and mice. These findings indicate that exercise training increases pulmonary expression of 11β-HSD1, thus contributing to local glucocorticoid activation and suppression of pulmonary inflammation in obese mice.
运动训练被提倡用于治疗慢性炎症和肥胖相关的代谢综合征。糖皮质激素（GCs）是抗炎激素，在肾上腺外器官中合成或代谢。本研究旨在探讨运动训练是否通过调节局部 GC 合成或代谢来影响与肥胖相关的肺炎症。我们发现，与瘦鼠相比，久坐肥胖（）小鼠的肺组织中白细胞介素（IL）-1β、IL-18、单核细胞趋化蛋白（MCP）-1和白细胞浸润水平升高，6 周运动训练可减轻这种情况。小鼠的肺皮质酮水平降低。运动训练增加了瘦鼠和肥胖鼠的肺皮质酮水平。肺皮质酮水平与 IL-1β、IL-18 和 MCP-1 呈负相关。成年小鼠肺组织切片的免疫组织化学染色显示类固醇急性调节蛋白、胆固醇侧链裂解酶（CYP11A1）、类固醇 21-羟化酶（CYP21）、3β-羟甾脱氢酶（3β-HSD）和 1 型和 2 型 11β-羟化酶（11β-HSD）的阳性免疫反应，但 11β-羟化酶（CYP11B1）无阳性免疫反应。运动训练显著增加了瘦鼠和肥胖鼠肺 11β-HSD1 的表达。相反，运动训练本身对肺 11β-HSD2 的表达没有影响，尽管肥胖鼠肺 11β-HSD2 水平明显高于瘦鼠。RU486，一种糖皮质激素受体拮抗剂，阻断了肥胖小鼠肺组织中运动训练的抗炎作用，并增加了瘦鼠运动后的炎性细胞因子。这些发现表明，运动训练增加了肺 11β-HSD1 的表达，从而促进了肥胖小鼠肺部 GC 的激活和肺部炎症的抑制。跑步机训练导致肥胖小鼠肺皮质酮水平显著升高，这与运动对肥胖相关肺部炎症的有利影响相一致。运动训练增加了瘦鼠和肥胖鼠肺 11β-羟化酶 1 型（11β-HSD1）的表达，但对肺 11β-HSD2 的表达没有显著影响。这些发现表明，运动训练增加了肺 11β-HSD1 的表达，从而促进了肥胖小鼠肺部 GC 的激活和肺部炎症的抑制。
