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

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 GCs synthesis or metabolism. We found that the sedentary obese (ob/ob) mice exhibited increased levels of interleukin (IL)-1β, IL-18, monocyte chemotactic protein (MCP)-1, and leukocyte infiltration in lung tissues compared with the lean mice, which was alleviated by 6 weeks of exercise training. Pulmonary corticosterone levels were decreased in the ob/ob mice. Exercise training increased pulmonary corticosterone levels in both lean and ob/ob mice. Pulmonary corticosterone levels were negative 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 (StAR) protein, the cholesterol side-chain-cleavage enzyme (CYP11A1), the steroid 21-hydroxylase (CYP21), 3β-hydroxysteroid dehydrogenase (3β-HSD), type I and type II 11β-hydroxysteroid dehydrogenase (11β-HSD), but not for 11β-hydroxylase (CYP11B1). Exercise training significantly increased pulmonary 11β-HSD1 expression in both the lean and ob/ob mice. In contrast, exercise training per se had no effect on pulmonary 11β-HSD2 expression, although pulmonary 11β-HSD2 levels in ob/ob mice were significantly higher than in the 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 GCs activation and suppression of pulmonary inflammation in obese mice.

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