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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

¹ Inserm "Avenir", Paris 6 University EA3502 and Human Research Center on Nutrition (CRNH), Hôtel Dieu Hospital, AP/HP, Paris, France
² SPIM "Santé publique et informatique médicale" laboratory, INSERM ERM202, Paris, France
³ INSERM UPS U586, Obesity Research Unit, Louis Bugnard Institute, Paul Sabatier University, Toulouse, France
⁴ Department of Anatomo-Pathology, Hôtel Dieu Hospital, Paris, France
⁵ Department of Surgery, Hôtel Dieu Hospital, Paris, France
⁶ Cardiovascular Physiology Department, J.-W. Goethe University, Frankfurt, Germany
⁷ Institute of Normal Human Morphology-Anatomy, School of Medicine, Polytechnic University of Marche, Ancona, Italy
⁸ Department of Internal Medicine, Research Centre for Endocrinology and Metabolism, Sahlgrenska Academy, Goteborg University, Goteborg, Sweden
⁹ Department of Pediatrics and Genetics, Howard Hugues Medical Institute, Beckman Center, Stanford University School of Medicine, Stanford, California
¹⁰ LIM & BIO, Paris-Nord University, Paris, France

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-1 [HIF-1]), 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-1 may play roles in the attraction of macrophages in scWAT.

Abbreviations: CRP, C-reactive protein; CSF, colony-stimulating factor; GO, Gene Ontology Consortium; FDR, false discovery rate; HIF-1, hypoxia-inducible factor-1; IL, interleukin; MCP, monocyte chemotactic protein; ORO, orosomucoid; PLAUR, plasminogen activator urokinase receptor; RTqPCR, real-time quantitative PCR; SAA, serum amyloid A; SAM, significance analysis of microarrays; scWAT, subcutaneous WAT; SVF, stroma vascular fraction; WAT, white adipose tissue

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