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Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss.

In human obesity, the stroma vascular fraction (SVF) of white adipose tissue (WAT) is enriched in macrophages. These cells may contribute to low-grade inflammation and to its metabolic complications. Little is known about the effect of weight loss on macrophages and genes involved in macrophage attraction. We examined subcutaneous WAT (scWAT) of 7 lean and 17 morbidly obese subjects before and 3 months after bypass surgery. Immunomorphological changes of the number of scWAT-infiltrating macrophages were evaluated, along with concomitant changes in expression of SVF-overexpressed genes. The number of scWAT-infiltrating macrophages before surgery was higher in obese than in lean subjects (HAM56+/CD68+; 22.6 +/- 4.3 vs. 1.4 +/- 0.6%, P < 0.001). Typical "crowns" of macrophages were observed around adipocytes. Drastic weight loss resulted in a significant decrease in macrophage number (-11.63 +/- 2.3%, P < 0.001), and remaining macrophages stained positive for the anti-inflammatory protein interleukin 10. Genes involved in macrophage attraction (monocyte chemotactic protein [MCP]-1, plasminogen activator urokinase receptor [PLAUR], and colony-stimulating factor [CSF]-3) and hypoxia (hypoxia-inducible factor-1alpha [HIF-1alpha]), expression of which increases in obesity and decreases after surgery, were predominantly expressed in the SVF. We show that improvement of the inflammatory profile after weight loss is related to a reduced number of macrophages in scWAT. MCP-1, PLAUR, CSF-3, and HIF-1alpha may play roles in the attraction of macrophages in scWAT.

Pubmed ID: 16046292

Authors

  • Cancello R
  • Henegar C
  • Viguerie N
  • Taleb S
  • Poitou C
  • Rouault C
  • Coupaye M
  • Pelloux V
  • Hugol D
  • Bouillot JL
  • Bouloumi√© A
  • Barbatelli G
  • Cinti S
  • Svensson PA
  • Barsh GS
  • Zucker JD
  • Basdevant A
  • Langin D
  • Cl√©ment K

Journal

Diabetes

Publication Data

August 27, 2005

Associated Grants

None

Mesh Terms

  • Adipose Tissue
  • Adult
  • Anastomosis, Roux-en-Y
  • Chemokine CCL2
  • Chemotactic Factors
  • DNA-Binding Proteins
  • Female
  • Gastric Bypass
  • Gene Expression
  • Granulocyte Colony-Stimulating Factor
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Macrophages
  • Middle Aged
  • Nuclear Proteins
  • Obesity, Morbid
  • Oligonucleotide Array Sequence Analysis
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Recombinant Proteins
  • Transcription Factors
  • Weight Loss