Reduction of Macrophage Infiltration and Chemoattractant Gene Expression Changes in White Adipose Tissue of Morbidly Obese Subjects After Surgery-Induced Weight Loss

  1. Raffaella Cancello1,
  2. Corneliu Henegar12,
  3. Nathalie Viguerie3,
  4. Soraya Taleb1,
  5. Christine Poitou1,
  6. Christine Rouault1,
  7. Muriel Coupaye1,
  8. Veronique Pelloux1,
  9. Danielle Hugol4,
  10. Jean-Luc Bouillot5,
  11. Anne Bouloumié36,
  12. Giorgio Barbatelli7,
  13. Saverio Cinti7,
  14. Per-Arne Svensson8,
  15. Gregory S. Barsh9,
  16. Jean-Daniel Zucker110,
  17. Arnaud Basdevant1,
  18. Dominique Langin3 and
  19. Karine Clément1
  1. 1Inserm “Avenir”, Paris 6 University EA3502 and Human Research Center on Nutrition (CRNH), Hôtel Dieu Hospital, AP/HP, Paris, France
  2. 2SPIM “Santé publique et informatique médicale” laboratory, INSERM ERM202, Paris, France
  3. 3INSERM UPS U586, Obesity Research Unit, Louis Bugnard Institute, Paul Sabatier University, Toulouse, France
  4. 4Department of Anatomo-Pathology, Hôtel Dieu Hospital, Paris, France
  5. 5Department of Surgery, Hôtel Dieu Hospital, Paris, France
  6. 6Cardiovascular Physiology Department, J.-W. Goethe University, Frankfurt, Germany
  7. 7Institute of Normal Human Morphology-Anatomy, School of Medicine, Polytechnic University of Marche, Ancona, Italy
  8. 8Department of Internal Medicine, Research Centre for Endocrinology and Metabolism, Sahlgrenska Academy, Goteborg University, Goteborg, Sweden
  9. 9Department of Pediatrics and Genetics, Howard Hugues Medical Institute, Beckman Center, Stanford University School of Medicine, Stanford, California
  10. 10LIM & BIO, Paris-Nord University, Paris, France
  1. Address correspondence and reprint requests to Karine Clément, MD, PhD, Department of Nutrition, Hôtel-Dieu Hospital, 1, Place du Parvis Notre-Dame, 75004 Paris, France. E-mail: karine.clement{at}htd.ap-hop-paris.fr

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

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted May 16, 2005.
    • Received January 17, 2005.
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  1. doi: 10.2337/diabetes.54.8.2277 Diabetes August 2005 vol. 54 no. 8 2277-2286
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