Contribution of glucocorticoid-mineralocorticoid receptor pathway on the obesity-related adipocyte dysfunction
| Autor: | Tohru Funahashi, Iichiro Shimomura, Ayumu Hirata, Hideaki Nakatsuji, Norikazu Maeda, Takuya Okada, Aki Hiuge-Shimizu |
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| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Biophysics Adipose tissue Adipokine Biology Spironolactone Biochemistry Body Mass Index chemistry.chemical_compound Mice Glucocorticoid receptor Mineralocorticoid receptor Receptors Glucocorticoid Adipokines Internal medicine Adipocyte 3T3-L1 Cells 11-beta-Hydroxysteroid Dehydrogenase Type 1 medicine Adipocytes Animals Humans Obesity RNA Small Interfering Receptor Molecular Biology Glucocorticoids Mineralocorticoid Receptor Antagonists Adiponectin Cell Biology Mice Mutant Strains Eplerenone Mifepristone Endocrinology Receptors Mineralocorticoid chemistry hormones hormone substitutes and hormone antagonists Glucocorticoid Metabolic Networks and Pathways medicine.drug |
| Zdroj: | Biochemical and biophysical research communications. 419(2) |
| ISSN: | 1090-2104 |
| Popis: | Aims Mineralocorticoid receptor (MR) blockade ameliorated insulin resistance with improvements in adipocytokine dysregulation, inflammation, and excess of reactive oxygen species (ROS) in obese adipose tissue and adipocytes, but its mechanism has not been clarified. The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), producing active glucocorticoids, is highly expressed in adipocytes and glucocorticoids bind to MR with higher affinity than to glucocorticoid receptor (GR). We investigated whether glucocorticoids effect on adipocytokines and ROS through MR in adipocytes. In addition, fat distributions of MR and GR were investigated in human subjects. Methods and Results Corticoid receptors and their target genes were examined in adipose tissue of obese db/db mice. 3T3-L1 adipocytes were treated with glucocorticoids, H2O2, MR antagonist eplerenone (EP), GR antagonist RU486 (RU), MR-siRNA, and/or N-acetylcysteine. Human adipose tissues were obtained from seven patients who underwent abdominal surgery. The mRNA levels of MR and its target gene were higher in db/db mice than in control db/m + mice. In 3T3-L1 adipocytes, glucocorticoids, similar to H2O2, caused the dysregulation of mRNA levels of various genes related to adipocytokines and the increase of intracellular ROS. Such changes were rectified by MR blockade, not by GR antagonist. In human fat, MR mRNA level was increased in parallel with the increase of body mass index (BMI) and its increase was more significant in visceral fat, while there were no apparent correlations of GR mRNA level to BMI or fat distribution. Conclusion Glucocorticoid-MR pathway may contribute to the obesity-related adipocytokine dysregulation and adipose ROS. |
| Databáze: | OpenAIRE |
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