title: Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss.
abstract: 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.
authors.affiliation: Inserm "Avenir", Paris 6 University EA3502 and Human Research Center on Nutrition (CRNH), Hôtel Dieu Hospital, AP/HP, Paris, France.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Cancello
authors.forename: Corneliu
authors.initials: C
authors.lastname: Henegar
authors.forename: Nathalie
authors.initials: N
authors.lastname: Viguerie
authors.forename: Soraya
authors.initials: S
authors.lastname: Taleb
authors.forename: Christine
authors.initials: C
authors.lastname: Poitou
authors.forename: Christine
authors.initials: C
authors.lastname: Rouault
authors.forename: Muriel
authors.initials: M
authors.lastname: Coupaye
authors.forename: Veronique
authors.initials: V
authors.lastname: Pelloux
authors.forename: Danielle
authors.initials: D
authors.lastname: Hugol
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Bouillot
authors.forename: Anne
authors.initials: A
authors.lastname: Bouloumié
authors.forename: Giorgio
authors.initials: G
authors.lastname: Barbatelli
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinti
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Svensson
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Barsh
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Zucker
authors.forename: Arnaud
authors.initials: A
authors.lastname: Basdevant
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
mesh_terms: 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
chemical_list: 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