In obese mice, exercise training increases 11β-HSD1 expression, contributing to glucocorticoid activation and suppression of pulmonary inflammation
| Autor: | Shu-Fang Du, Chang-Lin Ye, Shu-Juan Liu, Kai Chuan, Ze-Jia He, Yu-Jian Liu, Qing Yu, Xiaoyan Zhu |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty 3-Hydroxysteroid Dehydrogenases Physiology Interleukin-1beta Mice Obese Inflammation Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cytochrome P450 Family 21 Corticosterone Physiology (medical) Internal medicine 11-beta-Hydroxysteroid Dehydrogenase Type 2 Physical Conditioning Animal 11-beta-Hydroxysteroid Dehydrogenase Type 1 Medicine Animals Cholesterol Side-Chain Cleavage Enzyme Obesity Steroid 11-beta-hydroxylase Glucocorticoids Lung Chemokine CCL2 business.industry Interleukin-18 Pneumonia Mifepristone 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry Steroid 11-beta-Hydroxylase Interleukin 18 medicine.symptom business 030217 neurology & neurosurgery Glucocorticoid Hormone medicine.drug |
| Zdroj: | Journal of applied physiology (Bethesda, Md. : 1985). 123(4) |
| ISSN: | 1522-1601 |
| Popis: | 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 ( 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 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-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 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 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. NEW & NOTEWORTHY Treadmill training leads to a significant increase in pulmonary corticosterone levels in ob/ob 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 ob/ob 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. |
| Databáze: | OpenAIRE |
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