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Visfatin Is a Positive Regulator of MCP‐1 in Human Adipocytes In Vitro and in Mice In Vivo
Author(s) -
Sommer Grit,
Kralisch Susan,
Kloting Nora,
Kamprad Manja,
Schrock Kathleen,
Kratzsch Jurgen,
Tonjes Anke,
Lossner Ulrike,
Bluher Matthias,
Stumvoll Michael,
Fasshauer Mathias
Publication year - 2010
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2009.462
Subject(s) - nicotinamide phosphoribosyltransferase , endocrinology , medicine , adipokine , downregulation and upregulation , in vivo , proinflammatory cytokine , adipose tissue , adipocyte , secretion , monocyte , chemistry , insulin , inflammation , biology , insulin resistance , enzyme , biochemistry , nad+ kinase , gene , microbiology and biotechnology
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.