Macrophages and Adipocytes in Human Obesity

Adipose Tissue Gene Expression and Insulin Sensitivity During Calorie Restriction and Weight Stabilization

  1. Frédéric Capel1,2,3,
  2. Eva Klimčáková1,2,3,4,
  3. Nathalie Viguerie1,2,3,
  4. Balbine Roussel2,3,
  5. Michaela Vítková1,4,
  6. Michaela Kováčiková1,4,
  7. Jan Polák1,4,
  8. Zuzana Kováčová1,4,
  9. Jean Galitzky3,5,
  10. Jean-José Maoret2,3,
  11. Jiří Hanáček6,
  12. Tune H. Pers7,8,
  13. Anne Bouloumié3,5,
  14. Vladimir Štich1,4 and
  15. Dominique Langin1,2,3,9
  1. 1Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague, Czech Republic and Institut National de la Santé et de la Recherche Médicale, Toulouse, France;
  2. 2Institut National de la Santé et de la Recherche Médicale, U858, Obesity Research Laboratory, Rangueil Institute of Molecular Medicine, Toulouse, France;
  3. 3Paul Sabatier University, Louis Bugnard Institute, IFR31, Toulouse, France;
  4. 4Department of Sports Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic;
  5. 5Institut National de la Santé et de la Recherche Médicale, U858, AVENIR team “Vascular Network, Progenitor Cells and Immune Cells from Adipose Tissue,” Rangueil Institute of Molecular Medicine, Toulouse, France;
  6. 6Institute for Mother and Child Care, Prague, Czech Republic;
  7. 7Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark;
  8. 8Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark;
  9. 9Centre Hospitalier Universitaire de Toulouse, Biochemistry Laboratory, Biology Institute of Purpan, Toulouse, France.
  1. Corresponding author: Dominique Langin, dominique.langin{at}inserm.fr.
  1. F.C. and E.K. contributed equally to this study.

Abstract

OBJECTIVE We investigated the regulation of adipose tissue gene expression during different phases of a dietary weight loss program and its relation with insulin sensitivity.

RESEARCH DESIGN AND METHODS Twenty-two obese women followed a dietary intervention program composed of an energy restriction phase with a 4-week very-low-calorie diet and a weight stabilization period composed of a 2-month low-calorie diet followed by 3–4 months of a weight maintenance diet. At each time point, a euglycemic-hyperinsulinemic clamp and subcutaneous adipose tissue biopsies were performed. Adipose tissue gene expression profiling was performed using a DNA microarray in a subgroup of eight women. RT–quantitative PCR was used for determination of mRNA levels of 31 adipose tissue macrophage markers (n = 22).

RESULTS Body weight, fat mass, and C-reactive protein level decreased and glucose disposal rate increased during the dietary intervention program. Transcriptome profiling revealed two main patterns of variations. The first involved 464 mostly adipocyte genes involved in metabolism that were downregulated during energy restriction, upregulated during weight stabilization, and unchanged during the dietary intervention. The second comprised 511 mainly macrophage genes involved in inflammatory pathways that were not changed or upregulated during energy restriction and downregulated during weight stabilization and dietary intervention. Accordingly, macrophage markers were upregulated during energy restriction and downregulated during weight stabilization and dietary intervention. The increase in glucose disposal rates in each dietary phase was associated with variation in expression of sets of 80–110 genes that differed among energy restriction, weight stabilization, and dietary intervention.

CONCLUSIONS Adipose tissue macrophages and adipocytes show distinct patterns of gene regulation and association with insulin sensitivity during the various phases of a dietary weight loss program.

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.

    • Received January 8, 2009.
    • Accepted April 12, 2009.
  • Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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  1. Diabetes vol. 58 no. 7 1558-1567
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