title: Visfatin is a positive regulator of MCP-1 in human adipocytes in vitro and in mice in vivo.
abstract: Visfatin is a proinflammatory and potentially insulin-mimetic adipokine contributing to whole body glucose and lipid metabolism, as well as atherosclerosis. Monocyte chemoattractant protein (MCP)-1 is an adipocyte-secreted protein which might play a crucial role in metabolic and vascular disease. MCP-1 expression and secretion after visfatin treatment were determined by quantitative real-time reverse transcription-PCR and enzyme-linked immunosorbent assay (ELISA) in fully differentiated human mesenchymal stem cell-derived adipocytes (hMSC-Ads) in vitro. In addition, circulating levels of MCP-1 and visfatin were quantified by ELISA in 60 patients (30 nondiabetic, 30 diabetic) and MCP-1 serum levels in mice were determined after visfatin treatment in vivo. Interestingly, protein secretion and mRNA production of MCP-1 were induced significantly in hMSC-Ads after visfatin stimulation. Visfatin-induced MCP-1 secretion 1.9-fold after 8 h and 2.5-fold after 24 h relative to untreated cells (P < 0.05). MCP-1 mRNA synthesis was significantly stimulated by visfatin with maximal upregulation detectable at 250 ng/ml visfatin and after 4 h of treatment. Signaling studies suggested that p44/42 mitogen-activated protein (MAP) kinase is involved in visfatin-induced MCP-1 mRNA expression in hMSC-Ads. Detectability of visfatin in serum predicted circulating MCP-1 independent of age and gender in humans in vivo. MCP-1 serum levels were significantly increased more than twofold after visfatin treatment in mice in vivo. Taken together, our results demonstrate that visfatin upregulates MCP-1 supporting a possible role of MCP-1 in mediating the proinflammatory effects of visfatin.
authors.affiliation: Department of Internal Medicine III, University of Leipzig, Leipzig, Germany.
authors.forename: Grit
authors.initials: G
authors.lastname: Sommer
authors.forename: Susan
authors.initials: S
authors.lastname: Kralisch
authors.forename: Nora
authors.initials: N
authors.lastname: Kloting
authors.forename: Manja
authors.initials: M
authors.lastname: Kamprad
authors.forename: Kathleen
authors.initials: K
authors.lastname: Schrock
authors.forename: Jurgen
authors.initials: J
authors.lastname: Kratzsch
authors.forename: Anke
authors.initials: A
authors.lastname: Tonjes
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lossner
authors.forename: Matthias
authors.initials: M
authors.lastname: Bluher
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.forename: Mathias
authors.initials: M
authors.lastname: Fasshauer
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D018932:Chemokine CCL2; D012333:RNA, Messenger; D054409:Nicotinamide Phosphoribosyltransferase; D020928:Mitogen-Activated Protein Kinases