PMID- 17456576 OWN - NLM STAT- MEDLINE DCOM- 20070828 LR - 20151119 IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 92 IP - 7 DP - 2007 Jul TI - Monocyte chemoattractant protein-1 in subcutaneous abdominal adipose tissue: characterization of interstitial concentration and regulation of gene expression by insulin. PG - 2688-95 AB - 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-1alpha, 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. FAU - Murdolo, Giuseppe AU - Murdolo G AD - The Lundberg Laboratory for Diabetes Research, The Sahlgrenska Academy at Goteborg University, S-413 45 Goteborg, Sweden. giuseppe.murdolo@medic.gu.se FAU - Hammarstedt, Ann AU - Hammarstedt A FAU - Sandqvist, Madelene AU - Sandqvist M FAU - Schmelz, Martin AU - Schmelz M FAU - Herder, Christian AU - Herder C FAU - Smith, Ulf AU - Smith U FAU - Jansson, Per-Anders AU - Jansson PA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070424 PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Biomarkers) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Genetic Markers) RN - 0 (Insulin) SB - IM MH - Adipocytes/cytology/physiology MH - Adult MH - Biomarkers MH - Cell Size MH - Chemokine CCL2/*genetics MH - Diabetes Mellitus, Type 2/*genetics/immunology/physiopathology MH - Gene Expression Profiling MH - Gene Expression Regulation/immunology MH - *Genetic Markers MH - Humans MH - Hyperinsulinism/genetics/immunology/physiopathology MH - Insulin/*blood MH - Insulin Resistance MH - Male MH - Middle Aged MH - Obesity/genetics/immunology/physiopathology MH - Subcutaneous Fat/*physiology EDAT- 2007/04/26 09:00 MHDA- 2007/08/29 09:00 CRDT- 2007/04/26 09:00 PHST- 2007/04/26 09:00 [pubmed] PHST- 2007/08/29 09:00 [medline] PHST- 2007/04/26 09:00 [entrez] AID - jc.2006-2814 [pii] AID - 10.1210/jc.2006-2814 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2007 Jul;92(7):2688-95. doi: 10.1210/jc.2006-2814. Epub 2007 Apr 24.