scholarly journals Monocyte Chemoattractant Protein-1 Deficiency Fails to Restrain Macrophage Infiltration Into Adipose Tissue

Diabetes ◽  
2008 ◽  
Vol 57 (5) ◽  
pp. 1254-1261 ◽  
Author(s):  
E. A. Kirk ◽  
Z. K. Sagawa ◽  
T. O. McDonald ◽  
K. D. O'Brien ◽  
J. W. Heinecke
Endocrinology ◽  
2010 ◽  
Vol 151 (3) ◽  
pp. 971-979 ◽  
Author(s):  
Sanshiro Tateya ◽  
Yoshikazu Tamori ◽  
Takayuki Kawaguchi ◽  
Hajime Kanda ◽  
Masato Kasuga

Chronic inflammation in adipose tissue is thought to be important for the development of insulin resistance in obesity. Furthermore, the level of monocyte chemoattractant protein-1 (MCP-1) is increased not only in adipose tissue but also in the circulation in association with obesity. However, it has remained unclear to what extent the increased circulating level of MCP-1 contributes to insulin resistance. We have now examined the relevance of circulating MCP-1 to the development of insulin resistance in mice. The plasma concentration of MCP-1 was increased chronically or acutely in mice to the level observed in obese animals by chronic subcutaneous infusion of recombinant MCP-1 with an osmotic pump or by acute intravenous infusion of MCP-1 with an infusion pump, respectively. Whole-body metabolic parameters as well as inflammatory changes in adipose tissue were examined. A chronic increase in the circulating level of MCP-1 induced insulin resistance, macrophage infiltration into adipose tissue, and an increase in hepatic triacylglycerol content. An acute increase in the circulating MCP-1 concentration also induced insulin resistance but not macrophage infiltration into adipose tissue. In addition, inhibition of signaling by MCP-1 and its receptor CCR2 by administration of a novel CCR2 antagonist ameliorated insulin resistance in mice fed a high-fat diet without affecting macrophage infiltration into adipose tissue. These data indicate that an increase in the concentration of MCP-1 in the circulation is sufficient to induce systemic insulin resistance irrespective of adipose tissue inflammation.


2000 ◽  
Vol 58 (6) ◽  
pp. 2408-2419 ◽  
Author(s):  
Karl F. Hilgers ◽  
Andrea Hartner ◽  
Markus Porst ◽  
Monika Mai ◽  
Michael Wittmann ◽  
...  

Hepatology ◽  
2008 ◽  
Vol 48 (3) ◽  
pp. 799-807 ◽  
Author(s):  
Sophie Clément ◽  
Cristiana Juge-Aubry ◽  
Antonino Sgroi ◽  
Stéphanie Conzelmann ◽  
Valerio Pazienza ◽  
...  

2007 ◽  
Vol 92 (7) ◽  
pp. 2688-2695 ◽  
Author(s):  
Giuseppe Murdolo ◽  
Ann Hammarstedt ◽  
Madeléne Sandqvist ◽  
Martin Schmelz ◽  
Christian Herder ◽  
...  

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-1α, 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.


Sign in / Sign up

Export Citation Format

Share Document