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Göteborgs universitets publikationer

Monocyte chemoattractant protein-1 in subcutaneous abdominal adipose tissue: characterization of interstitial concentration and regulation of gene expression by insulin

Författare och institution:
Giuseppe Murdolo (Institutionen för medicin, avdelningen för molekylär och klinisk medicin); Ann Hammarstedt (Institutionen för medicin, avdelningen för molekylär och klinisk medicin); Madelene Sandqvist (Institutionen för medicin, avdelningen för molekylär och klinisk medicin); M. Schmelz (-); C. Herder (-); Ulf Smith (Institutionen för medicin, avdelningen för molekylär och klinisk medicin); Per-Anders Jansson (Institutionen för medicin, avdelningen för molekylär och klinisk medicin)
Publicerad i:
J Clin Endocrinol Metab, 92 ( 7 ) s. 2688-95
0021-972X (Print)
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Adipocytes/cytology/physiology, Adult, Biological Markers, Cell Size, Chemokine CCL2/*genetics, Diabetes Mellitus, Type 2/*genetics/immunology/physiopathology, Gene Expression Profiling, Gene Expression Regulation/immunology, *Genetic Markers, Humans, Hyperinsulinism/genetics/immunology/physiopathology, Insulin/*blood, Insulin Resistance, Male, Middle Aged, Obesity/genetics/immunology/physiopathology, Subcutaneous Fat/*physiology
Postens nummer:
Posten skapad:
2007-09-27 14:04
Posten ändrad:
2010-01-26 12:43

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