Isoproterenol stimulates monocyte chemoattractant protein-1 expression and secretion in 3T3-L1 adipocytes.
Recently, monocyte chemoattractant protein (MCP)-1 has been characterized as a novel adipocytokine upregulated in obesity and insulin resistance which impairs insulin signaling in muscle and fat in vitro. Growing evidence, on the other hand, suggests that increased activity of the sympathetic nervous system is an integral part in the development of insulin resistance. In the current study, the impact of the beta-adrenergic agonist isoproterenol on MCP-1 mRNA synthesis and secretion was determined in 3T3-L1 adipocytes. Interestingly, isoproterenol increased MCP-1 secretion 3-fold. Furthermore, 10 microM isoproterenol acutely induced MCP-1 mRNA by up to 5.3-fold in a time-dependent fashion with significant stimulation seen at concentrations as low as 0.3 microM effector. Studies using pharmacological inhibitors suggested that basal and isoproterenol-induced MCP-1 expressions are mediated via beta-adrenergic receptors and protein kinase A. Moreover, acute activation of adenylyl cyclase by forskolin was sufficient to mimic the effects of isoproterenol. Taken together, our results demonstrate that isoproterenol induces MCP-1 expression and secretion via a classical GS-protein-coupled pathway and support the notion that MCP-1 might be an interesting novel candidate linking obesity and insulin resistance.
Kralisch
Susan
S
University of Leipzig, Department of Internal Medicine III, 04103 Leipzig, Germany.
Klein
Johannes
J
Lossner
Ulrike
U
Bluher
Matthias
M
Paschke
Ralf
R
Stumvoll
Michael
M
Fasshauer
Mathias
M
D016475:3T3 Cells; D000262:Adenylyl Cyclases / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D007545:Isoproterenol / Q000494:pharmacology*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism
D000318:Adrenergic beta-Agonists; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D012333:RNA, Messenger; D005576:Colforsin; D000262:Adenylyl Cyclases; D007545:Isoproterenol