Tissue inhibitor of metalloproteinase 1 expression and secretion are induced by beta-adrenergic stimulation in 3T3-L1 adipocytes.
Tissue inhibitor of metalloproteinase (TIMP)-1 is an adipocytokine upregulated in obesity which might promote adipose tissue development. In the current study, the impact of the beta-adrenergic agonist isoproterenol on TIMP-1 gene expression and secretion was determined in 3T3-L1 adipocytes. Interestingly, isoproterenol increased TIMP-1 secretion 2.7-fold. Furthermore, isoproterenol induced TIMP-1 mRNA in a time- and dose-dependent fashion with significant effects observed as early as 1 h after effector addition and at concentrations as low as 1 microM isoproterenol. Significant isoproterenol-induced upregulation of TIMP-1 mRNA could also be found in immortalized brown adipocytes. Inhibitor experiments confirmed that the positive effect of isoproterenol on TIMP-1 is mediated via beta-adrenergic receptors and protein kinase A. Moreover, increasing cAMP levels with forskolin or dibutyryl-cAMP was sufficient to stimulate TIMP-1 synthesis. Insulin induced basal TIMP-1 mRNA, but did not significantly influence forskolin-induced TIMP-1 expression. Taken together, we demonstrate that TIMP-1 expression and secretion are selectively upregulated in adipocytes by beta-adrenergic agonists via a classic Gs-protein-coupled pathway.
Kralisch
S
S
University of Leipzig, Department of Internal Medicine III, Ph-Rosenthal-Str. 27, 04103 Leipzig, Germany.
Lossner
U
U
Bluher
M
M
Paschke
R
R
Stumvoll
M
M
Fasshauer
M
M
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002461:Cell Line, Transformed; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013268:Stimulation, Chemical; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D000318:Adrenergic beta-Agonists; D007328:Insulin; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D005576:Colforsin; D003994:Bucladesine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol