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Monocyte Chemoattractant Protein-1 in Subcutaneous Abdominal Adipose Tissue: Characterization of Interstitial Concentration and Regulation of Gene Expression by Insulin

The Lundberg Laboratory for Diabetes Research (G.M., A.H., M.Sa., U.S., P.-A.J.), Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at Göteborg University, S-413 45 Göteborg, Sweden; Department of Internal Medicine (G.M.), Section of Internal Medicine, Endocrine and Metabolic Sciences, Perugia University, I-06122, Perugia, Italy; Department of Anesthesiology and Intensive Care Medicine Mannheim (M.Sc.), University of Heidelberg, 368 D-69120 Heidelberg, Germany; and German Diabetes Clinic (C.H.), German Diabetes Center, Leibniz Center at Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany

Address all correspondence and requests for reprints to: Giuseppe Murdolo, M.D., Ph.D., Department of Internal Medicine, Division of Endocrinology and Metabolism, Via Enrico Dal Pozzo, I-06122 Perugia, Italy. E-mail: giuseppe.murdolo{at}medic.gu.se; gmurdolo{at}tiscalinet.it.

Context: The chemokine monocyte chemoattractant protein-1 (MCP-1) is implicated in obesity-associated chronic inflammation, insulin resistance, and atherosclerosis.

Objectives: The objectives of this study were to: 1) characterize the interstitial levels and the gene expression of MCP-1 in the sc abdominal adipose tissue (SCAAT), 2) elucidate the response of MCP-1 to acute hyperinsulinemia, and 3) determine the relationship between MCP-1 and arterial stiffness.

Design: Nine lean (L) and nine uncomplicated obese (OB) males were studied in the fasting state and during a euglycemic-hyperinsulinemic clamp combined with the microdialysis technique. Interstitial and serum MCP-1 (iMCP-1 and sMCP-1, respectively) levels, pulse wave analysis, and SCAAT biopsies were characterized at baseline and after hyperinsulinemia.

Results: OB showed elevated sMCP-1 (P < 0.01) but similar iMCP-1 levels as compared with L. Basal iMCP-1 concentrations were considerably higher than sMCP-1 (P < 0.0001), and a gradient between iMCP-1 and sMCP-1 levels was maintained throughout the hyperinsulinemia. At baseline, SCAAT gene expression profile revealed a "co-upregulation" of MCP-1, MCP-2, macrophage inflammatory protein-1, and CD68 in OB, and whole-body glucose disposal inversely correlated with the MCP-1 gene expression. After hyperinsulinemia, MCP-1 and MCP-2 mRNA levels significantly increased in L, but not in OB. Finally, sMCP-1 excess in the OB positively correlated with the stiffer vasculature.

Conclusions: These observations demonstrate similar interstitial concentrations and a differential gene response to hyperinsulinemia of MCP-1 in the SCAAT from L and OB individuals. In human obesity, we suggest the SCAAT MCP-1 gene overexpression as a biomarker of an "inflamed" adipose organ and impaired glucose metabolism.

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