title: Monocyte chemoattractant protein-1 in subcutaneous abdominal adipose tissue: characterization of interstitial concentration and regulation of gene expression by insulin.
abstract: BACKGROUND
  The chemokine monocyte chemoattractant protein-1 (MCP-1) is implicated in obesity-associated chronic inflammation, insulin resistance, and atherosclerosis.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
authors: The Lundberg Laboratory for Diabetes Research, The Sahlgrenska Academy at Göteborg University, S-413 45 Göteborg, Sweden. giuseppe.murdolo@medic.gu.se
authors: Giuseppe
authors: G
authors: Murdolo
authors: Ann
authors: A
authors: Hammarstedt
authors: Madeléne
authors: M
authors: Sandqvist
authors: Martin
authors: M
authors: Schmelz
authors: Christian
authors: C
authors: Herder
authors: Ulf
authors: U
authors: Smith
authors: Per-Anders
authors: PA
authors: Jansson
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000502:physiology; D000328:Adult; D015415:Biomarkers; D048429:Cell Size; D018932:Chemokine CCL2 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D005819:Genetic Markers; D006801:Humans; D006946:Hyperinsulinism / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D050151:Subcutaneous Fat / Q000502:physiology*
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D005819:Genetic Markers; D007328:Insulin