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.
Cancello
Raffaella
R
Inserm "Avenir", Paris 6 University EA3502 and Human Research Center on Nutrition (CRNH), Hôtel Dieu Hospital, AP/HP, Paris, France.
Henegar
Corneliu
C
Viguerie
Nathalie
N
Taleb
Soraya
S
Poitou
Christine
C
Rouault
Christine
C
Coupaye
Muriel
M
Pelloux
Veronique
V
Hugol
Danielle
D
Bouillot
Jean-Luc
JL
Bouloumié
Anne
A
Barbatelli
Giorgio
G
Cinti
Saverio
S
Svensson
Per-Arne
PA
Barsh
Gregory S
GS
Zucker
Jean-Daniel
JD
Basdevant
Arnaud
A
Langin
Dominique
D
Clément
Karine
K
D000273:Adipose Tissue / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000713:Anastomosis, Roux-en-Y; D018932:Chemokine CCL2 / Q000235:genetics; D002630:Chemotactic Factors / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D000069585:Filgrastim; D015390:Gastric Bypass; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008264:Macrophages / Q000473:pathology*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D009767:Obesity, Morbid / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D020411:Oligonucleotide Array Sequence Analysis; D011956:Receptors, Cell Surface / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; D014157:Transcription Factors / Q000235:genetics; D015431:Weight Loss
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D002630:Chemotactic Factors; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; D014157:Transcription Factors; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim