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Submitted on December 19, 2006
Accepted on April 12, 2007
The Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden; Department of Internal Medicine, Section of Internal Medicine, Endocrine and Metabolic Sciences, Perugia University, Perugia, Italy; Department of Anesthesiology and Intensive Care Medicine Mannheim, University of Heidelberg, Heidelberg, Germany; German Diabetes Clinic, German Diabetes Center, Leibniz Center at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
* To whom correspondence should be addressed. E-mail: TUgiuseppe.murdolo{at}medic.gu.seUT.
Context: The chemokine monocyte chemoattractant protein-1 (MCP-1) is implicated in the obesity-associated chronic inflammation, insulin resistance, and atherosclerosis.
Objectives: The objectives of this study were: 1) to characterize the interstitial levels and the gene expression of MCP-1 in the subcutaneous abdominal adipose tissue (SCAAT); 2) to elucidate the response of MCP-1 to acute hyperinsulinemia and; 3) to 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 (i) and serum (s) MCP-1 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 interstitial and serum MCP-1 levels was maintained throughout the hyperinsulinemia. At baseline, SCAAT gene expression profile revealed a "co-upregulation" of MCP-1, MCP-2, MIP-1
, and CD68 in OB, and whole-body glucose disposal inversely correlated with the MCP-1 gene expression. Following 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 lean and obese individuals. In human obesity, we suggest the SCAAT MCP-1 gene over-expression as a biomarker of an "inflamed" adipose organ and impaired glucose metabolism.
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