In obese mice, exercise training increases 11 beta-HSD1 expression, contributing to glucocorticoid activation and suppression of pulmonary inflammation

摘要

Exercise training is advocated for treating chronic inflammation and obesity-related metabolic syndromes. Glucocorticoids (GCs), the antiinflammatory hormones, are synthesized or metabolized in extraadrenal 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 (ob/ob) mice exhibited increased levels of interleukin (IL)-1 beta, 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 ob/ob mice. Exercise training increased pulmonary corticosterone levels in both lean and ob/ob mice. Pulmonary corticosterone levels were negatively correlated with IL-1 beta, 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), 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), and type 1 and type 2 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) but not for 11 beta-hydroxylase (CYP11B1). Exercise training significantly increased pulmonary 11 beta-HSD1 expression in both lean and ob/ob mice. In contrast, exercise training per se had no effect on pulmonary 11 beta-HSD2 expression, although pulmonary 11 beta-HSD2 levels in ob/ob 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 11 beta-HSD1, thus contributing to local GC activation and suppression of pulmonary inflammation in obese mice.