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Department of Medicine, Huddinge, Karolinska Institute (I.D., M.K., K.W., E.A.N., L.B., P.A.), SE-14186 Stockholm, Sweden; Biovitrum AB (A.S., M.F., A.A.), SE-11276 Stockholm, Sweden; Department of Medicine, Umea University Hospital (T.O., J.A.), SE-90187 Umea, Sweden; and Oxford Center for Diabetes, Endocrinology, and Metabolism, Churchill Hospital (G.D.T., A.S.T.B.), Oxford OX3 7LJ, United Kingdom
Address all correspondence and requests for reprints to: Dr. Peter Arner, Department of Medicine, M61, Karolinska University Hospital, SE-14186 Huddinge, Sweden. E-mail: peter.arner{at}medhs.ki.se.
Context: Low-grade inflammation in adipose tissue may contribute to insulin resistance in obesity. However, the roles of individual inflammatory mediators in adipose tissue are poorly understood.
Objectives: The objective of this study was to determine which inflammation markers are most overexpressed at the gene level in adipose tissue in human obesity and how this relates to corresponding protein secretion.
Design: We examined gene expression profiles in 17 lean and 20 obese subjects. The secretory pattern of relevant corresponding proteins was examined in human sc adipose tissue or isolated fat cells in vitro and in vivo in several obese or lean cohorts.
Results: In ranking gene expression, defined pathways associated with obesity and immune and defense responses scored high. Among seven markedly overexpressed chemokines, only monocyte chemoattractant protein 1 (MCP1) was released from adipose tissue and isolated fat cells in vitro. In obesity, the secretion and expression of MCP1 in adipose tissue pieces were more than 6- and 2-fold increased, respectively, but there was no change in circulating MCP1 levels. There was no net release of MCP1, but there was a net release of leptin, in vivo from adipose tissue into the circulation.
Conclusions: Obesity is associated with the increased expression of several chemokine genes in adipose tissue. However, only MCP1 is secreted into the extracellular space, where it primarily acts as a local factor, because little or no spillover into the circulation occurs. MCP1 influences the function of adipocytes, is a recruitment factor for macrophages, and may be a crucial link among chemokines between adipose tissue inflammation and insulin resistance.
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