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Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women

Abstract

Objective:

Accumulation of adipose tissue macrophages (ATMs) is observed in obesity and may participate in the development of insulin resistance and obesity-related complications. The aim of our study was to investigate the effect of long-term dietary intervention on ATM content in human adipose tissue.

Design:

We performed a multi-phase longitudinal study.

Subjects and measurements:

A total of 27 obese pre-menopausal women (age 39±2 years, body mass index 33.7±0.5 kg m–2) underwent a 6-month dietary intervention consisting of two periods: 4 weeks of very low-calorie diet (VLCD) followed by weight stabilization composed of 2 months of low-calorie diet and 3to 4 months of weight maintenance diet. At baseline and at the end of each dietary period, samples of subcutaneous adipose tissue (SAT) were obtained by needle biopsy and blood samples were drawn. ATMs were determined by flow cytometry using combinations of cell surface markers. Selected cytokine and chemokine plasma levels were measured using enzyme-linked immunosorbent assay. In addition, in a subgroup of 16 subjects, gene expression profiling of macrophage markers in SAT was performed using real-time PCR.

Results:

Dietary intervention led to a significant decrease in body weight, plasma insulin and C-reactive protein levels. After VLCD, ATM content defined by CD45+/14+/206+ did not change, whereas it decreased at the end of the intervention. This decrease was associated with a downregulation of macrophage marker mRNA levels (CD14, CD163, CD68 and LYVE-1 (lymphatic vessel endothelial hyaluronan receptor-1)) and plasma levels of monocyte-chemoattractant protein-1 (MCP-1) and CXCL5 (chemokine (C-X-C motif) ligand 5). During the whole dietary intervention, the proportion of two ATM subpopulations distinguished by the CD16 marker was not changed.

Conclusion:

A 6-month weight-reducing dietary intervention, but not VLCD, promotes a decrease in the number of the whole ATM population with no change in the relative distribution of ATM subsets.

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References

  1. Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C et al. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 2005; 54: 2277–2286.

    Article  CAS  Google Scholar 

  2. Duffaut C, Zakaroff-Girard A, Bourlier V, Decaunes P, Maumus M, Chiotasso P et al. Interplay between human adipocytes and T lymphocytes in obesity. CCL20 as an adipochemokine and T lymphocytes as lipogenic modulators. Arterioscler Thromb Vasc Biol 2009; 29: 1608–1614.

    Article  CAS  Google Scholar 

  3. Elgazar-Carmon V, Rudich A, Hadad N, Levy R . Neutrophils transiently infiltrate intra-abdominal fat early in the course of high-fat feeding. J Lipid Res 2008; 49: 1894–1903.

    Article  CAS  Google Scholar 

  4. Kintscher U, Hartge M, Hess K, Foryst-Ludwig A, Clemenz M, Wabitsch M et al. T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol 2008; 28: 1304–1310.

    Article  CAS  Google Scholar 

  5. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante Jr AW . Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112: 1796–1808.

    Article  CAS  Google Scholar 

  6. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003; 112: 1821–1830.

    Article  CAS  Google Scholar 

  7. Heilbronn LK, Campbell LV . Adipose tissue macrophages, low grade inflammation and insulin resistance in human obesity. Curr Pharm Des 2008; 14: 1225–1230.

    Article  CAS  Google Scholar 

  8. Hotamisligil GS . Inflammation and metabolic disorders. Nature 2006; 444: 860–867.

    Article  CAS  Google Scholar 

  9. Poitou C, Coussieu C, Rouault C, Coupaye M, Cancello R, Bedel JF et al. Serum amyloid A: a marker of adiposity-induced low-grade inflammation but not of metabolic status. Obesity (Silver Spring) 2006; 14: 309–318.

    Article  CAS  Google Scholar 

  10. Bourlier V, Zakaroff-Girard A, Miranville A, De Barros S, Maumus M, Sengenes C et al. Remodeling phenotype of human subcutaneous adipose tissue macrophages. Circulation 2008; 117: 806–815.

    Article  CAS  Google Scholar 

  11. Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW . Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 2004; 145: 2273–2282.

    Article  CAS  Google Scholar 

  12. Maury E, Ehala-Aleksejev K, Guiot Y, Detry R, Vandenhooft A, Brichard SM . Adipokines oversecreted by omental adipose tissue in human obesity. Am J Physiol Endocrinol Metab 2007; 293: E656–E665.

    Article  CAS  Google Scholar 

  13. Shoelson SE, Herrero L, Naaz A . Obesity, inflammation, and insulin resistance. Gastroenterology 2007; 132: 2169–2180.

    Article  CAS  Google Scholar 

  14. Cancello R, Tordjman J, Poitou C, Guilhem G, Bouillot JL, Hugol D et al. Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity. Diabetes 2006; 55: 1554–1561.

    Article  CAS  Google Scholar 

  15. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005; 46: 2347–2355.

    Article  CAS  Google Scholar 

  16. Ortega Martinez de Victoria E, Xu X, Koska J, Francisco AM, Scalise M, Ferrante Jr AW et al. Macrophage content in subcutaneous adipose tissue: associations with adiposity, age, inflammatory markers, and whole-body insulin action in healthy Pima Indians. Diabetes 2009; 58: 385–393.

    Article  Google Scholar 

  17. Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R et al. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 2006; 116: 1494–1505.

    Article  CAS  Google Scholar 

  18. Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, Vaddi K et al. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 2006; 116: 115–124.

    Article  CAS  Google Scholar 

  19. Lumeng CN, Deyoung SM, Saltiel AR . Macrophages block insulin action in adipocytes by altering expression of signaling and glucose transport proteins. Am J Physiol Endocrinol Metab 2007; 292: E166–E174.

    Article  CAS  Google Scholar 

  20. Nguyen MT, Favelyukis S, Nguyen AK, Reichart DD, Scott PA, Jenn A et al. A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways. J Biol Chem 2007; 282: 35279–35292.

    Article  CAS  Google Scholar 

  21. Apovian CM, Bigornia S, Mott M, Meyers MR, Ulloor J, Gagua M et al. Adipose macrophage infiltration is associated with insulin resistance and vascular endothelial dysfunction in obese subjects. Arterioscler Thromb Vasc Biol 2008; 28: 1654–1659.

    Article  CAS  Google Scholar 

  22. Cipolletta C, Ryan KE, Hanna EV, Trimble ER . Activation of peripheral blood CD14+ monocytes occurs in diabetes. Diabetes 2005; 54: 2779–2786.

    Article  CAS  Google Scholar 

  23. Tordjman J, Poitou C, Hugol D, Bouillot JL, Basdevant A, Bedossa P et al. Association between omental adipose tissue macrophages and liver histopathology in morbid obesity: influence of glycemic status. J Hepatol 2009; 51: 354–362.

    Article  CAS  Google Scholar 

  24. Curat CA, Miranville A, Sengenes C, Diehl M, Tonus C, Busse R et al. From blood monocytes to adipose tissue-resident macrophages: induction of diapedesis by human mature adipocytes. Diabetes 2004; 53: 1285–1292.

    Article  CAS  Google Scholar 

  25. Mosser DM, Edwards JP . Exploring the full spectrum of macrophage activation. Nat Rev Immunol 2008; 8: 958–969.

    Article  CAS  Google Scholar 

  26. Stout RD, Suttles J . Functional plasticity of macrophages: reversible adaptation to changing microenvironments. J Leukoc Biol 2004; 76: 509–513.

    Article  CAS  Google Scholar 

  27. Lumeng CN, Bodzin JL, Saltiel AR . Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 2007; 117: 175–184.

    Article  CAS  Google Scholar 

  28. Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR . Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 2008; 57: 3239–3246.

    Article  CAS  Google Scholar 

  29. Bourlier V, Bouloumie A . Role of macrophage tissue infiltration in obesity and insulin resistance. Diabetes Metab 2009; 35: 251–260.

    Article  CAS  Google Scholar 

  30. Zeyda M, Farmer D, Todoric J, Aszmann O, Speiser M, Gyori G et al. Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production. Int J Obes (Lond) 2007; 31: 1420–1428.

    Article  CAS  Google Scholar 

  31. Klimcakova E, Polak J, Moro C, Hejnova J, Majercik M, Viguerie N et al. Dynamic strength training improves insulin sensitivity without altering plasma levels and gene expression of adipokines in subcutaneous adipose tissue in obese men. J Clin Endocrinol Metab 2006; 91: 5107–5112.

    Article  CAS  Google Scholar 

  32. Miranville A, Heeschen C, Sengenes C, Curat CA, Busse R, Bouloumie A . Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation 2004; 110: 349–355.

    Article  CAS  Google Scholar 

  33. Capel F, Klimcakova E, Viguerie N, Roussel B, Vitkova M, Kovacikova M et al. Macrophages and adipocytes in human obesity: adipose tissue gene expression and insulin sensitivity during calorie restriction and weight stabilization. Diabetes 2009; 58: 1558–1567.

    Article  CAS  Google Scholar 

  34. Chavey C, Lazennec G, Lagarrigue S, Clape C, Iankova I, Teyssier J et al. CXC ligand 5 is an adipose-tissue derived factor that links obesity to insulin resistance. Cell Metab 2009; 9: 339–349.

    Article  CAS  Google Scholar 

  35. Conti P, DiGioacchino M . MCP-1 and RANTES are mediators of acute and chronic inflammation. Allergy Asthma Proc 2001; 22: 133–137.

    Article  CAS  Google Scholar 

  36. Walz A, Schmutz P, Mueller C, Schnyder-Candrian S . Regulation and function of the CXC chemokine ENA-78 in monocytes and its role in disease. J Leukoc Biol 1997; 62: 604–611.

    Article  CAS  Google Scholar 

  37. Klimcakova E, Kovacikova M, Stich V, Langin D . Adipokines and dietary interventions in human obesity. Obes Rev 2010 (e-pub ahead of print).

  38. Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS et al. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab 1997; 82: 4196–4200.

    CAS  Google Scholar 

  39. Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM et al. IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 2005; 11: 191–198.

    Article  CAS  Google Scholar 

  40. Varma V, Yao-Borengasser A, Rasouli N, Nolen GT, Phanavanh B, Starks T et al. Muscle inflammatory response and insulin resistance: synergistic interaction between macrophages and fatty acids leads to impaired insulin action. Am J Physiol Endocrinol Metab 2009; 296: E1300–E1310.

    Article  CAS  Google Scholar 

  41. Suganami T, Nishida J, Ogawa Y . A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arterioscler Thromb Vasc Biol 2005; 25: 2062–2068.

    Article  CAS  Google Scholar 

  42. Surmi BK, Hasty AH . Macrophage infiltration into adipose tissue: initiation, propagation and remodeling. Future Lipidol 2008; 3: 545–556.

    Article  CAS  Google Scholar 

  43. Gordon S . Alternative activation of macrophages. Nat Rev Immunol 2003; 3: 23–35.

    Article  CAS  Google Scholar 

  44. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M . The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 2004; 25: 677–686.

    Article  CAS  Google Scholar 

  45. Martinez FO, Sica A, Mantovani A, Locati M . Macrophage activation and polarization. Front Biosci 2008; 13: 453–461.

    Article  CAS  Google Scholar 

  46. Geissmann F, Jung S, Littman DR . Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 2003; 19: 71–82.

    Article  CAS  Google Scholar 

  47. Rogacev KS, Ulrich C, Blomer L, Hornof F, Oster K, Ziegelin M et al. Monocyte heterogeneity in obesity and subclinical atherosclerosis. Eur Heart J 2010; 31: 369–376.

    Article  CAS  Google Scholar 

  48. Ziegler-Heitbrock L . The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J Leukoc Biol 2007; 81: 584–592.

    Article  CAS  Google Scholar 

  49. McGrath MS, Kodelja V . Balanced macrophage activation hypothesis: a biological model for development of drugs targeted at macrophage functional states. Pathobiology 1999; 67: 277–281.

    Article  CAS  Google Scholar 

  50. Zeyda M, Stulnig TM . Adipose tissue macrophages. Immunol Lett 2007; 112: 61–67.

    Article  CAS  Google Scholar 

  51. Aron-Wisnewsky J, Tordjman J, Poitou C, Darakhshan F, Hugol D, Basdevant A et al. Human adipose tissue macrophages: M1 and M2 cell surface markers in subcutaneous and omental depots and after weight loss. J Clin Endocrinol Metab 2009; 94: 4619–4623.

    Article  CAS  Google Scholar 

  52. Bouhlel MA, Derudas B, Rigamonti E, Dievart R, Brozek J, Haulon S et al. PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab 2007; 6: 137–143.

    Article  CAS  Google Scholar 

  53. Deguchi JO, Yamazaki H, Aikawa E, Aikawa M . Chronic hypoxia activates the Akt and beta-catenin pathways in human macrophages. Arterioscler Thromb Vasc Biol 2009; 29: 1664–1670.

    Article  CAS  Google Scholar 

  54. Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L et al. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 2007; 447: 1116–1120.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Zuzana Parizkova for her excellent technical assistance and Dr Zdenka Prochazkova for laboratory analysis. This work was supported by Grant IGA NS 10519-3-2009 of Ministry of Health of the Czech Republic, by research project of MSMT of the Czech Republic MSM 0021620814, by INSERM and by the Commission of the European Communities (Integrated Project HEPADIP (http://www.hepadip.org), Contract LSHM-CT-2005-018734, and Collaborative Project ADAPT (http://www.adapt-eu.net), Contract HEALTH F2-2008-2011 00).

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Correspondence to M Kováčiková.

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Kováčiková, M., Sengenes, C., Kováčová, Z. et al. Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women. Int J Obes 35, 91–98 (2011). https://doi.org/10.1038/ijo.2010.112

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  • DOI: https://doi.org/10.1038/ijo.2010.112

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