title: Aldosterone perturbs adiponectin and PAI-1 expression and secretion in 3T3-L1 adipocytes.
abstract: Aldosterone is considered as a new cardiovascular risk factor that plays an important role in metabolic syndrome; however, the underlying mechanism of these effects is not clear. Hypoadiponectinemia and elevated circulating concentration of plasminogen activator inhibitor-1 (PAI-1) are causally associated with obesity-related insulin resistance and cardiovascular disease. The aim of the present study is to investigate the effect of aldosterone on the production of adiponectin and PAI-1 in 3T3-L1 adipocytes. Northern and Western blot analyses revealed that aldosterone treatment inhibited adiponectin mRNA expression and secretion and simultaneously enhanced PAI-1 mRNA expression and secretion in a time- and dose-dependent manner. Rosiglitazone did not prevent aldosterone's effect on adiponectin or PAI-1 expression. In contrast, tumor necrosis factor (TNF)-α produced dramatic synergistic effects on adiponectin and PAI-1 expression when added together with aldosterone. Furthermore, the effects of aldosterone on adiponectin and PAI-1 expression appear to be mediated through glucocorticoid receptor (GR) but not mineralocorticoid receptor (MR). These results suggest that the effects of aldosterone on adiponectin and PAI-1 production are one of the underlying mechanisms linking it to insulin resistance, metabolic syndrome and cardiovascular disease.
authors.affiliation: Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, PR China.
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.forename: X-N
authors.initials: XN
authors.lastname: Zhang
authors.forename: C-M
authors.initials: CM
authors.lastname: Pan
authors.forename: F
authors.initials: F
authors.lastname: Sun
authors.forename: D-L
authors.initials: DL
authors.lastname: Zhu
authors.forename: H-D
authors.initials: HD
authors.lastname: Song
authors.forename: M-D
authors.initials: MD
authors.lastname: Chen
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics* / Q000378:metabolism*; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D000451:Mineralocorticoid Receptor Antagonists; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D013997:Time Factors
chemical_list: D052242:Adiponectin; D000451:Mineralocorticoid Receptor Antagonists; D047495:PPAR gamma; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone