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M1 Polarized Macrophages Persist in Skin of Post-Bariatric Patients after 2 Years

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Abstract

Background

Obesity is considered a condition of systemic chronic inflammation. Under this condition, adipose tissue macrophages switch from an M2 (anti-inflammatory) activation pattern to an M1 (proinflammatory) activation pattern.

Objective

The study aimed to verify the profile of skin macrophage activation after bariatric surgery as well as the role of MMP-1 in extracellular tissue remodeling.

Methods

This is a prospective, controlled and comparative study with 20 individuals split into two groups according to their skin condition: post-bariatric and eutrophic patients. Histological and morphometric analyses based on hematoxylin-eosin, picrosirius red (collagen), orcein (elastic fiber systems), and alcian blue (mast cells)-stained sections and immunohistochemical analysis (CD68, iNOS, and mannose receptor) for macrophages and metalloproteinase-1 were performed.

Results

Post-bariatric skin showed an increase in inflammation, angiogenesis, CD68, M1 macrophages (P< 0.001), and mast cells (P< 0.01); a decrease in M2 macrophages (P< 0.01); and a significant decrease in the collagen fiber network (P< 0.001). MMP-1 was increased in the papillary dermis of post-bariatric skin and decreased in the epidermis compared to eutrophic skin (P< 0.05).

Conclusion

This study shows that post-bariatric skin maintains inflammatory characteristics for two years. Mast cells and M1 macrophages maintain and enhance the remodeling of the dermal extracellular matrix initiated during obesity in part due to the presence of MMP-1 in the papillary dermis.

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References

  1. Kelly T, Yang W, Chen C-S, Reynolds K, He J (2008) Global burden of obesity in 2005 and projections to 2030. Int J Obes 32:1432–1437. https://doi.org/10.1038/ijo.2008.102

    Article  Google Scholar 

  2. Johnson AR, Milner JJ, Makowski L (2012) The inflammation highway: metabolism accelerates inflammatory traffic in obesity. Immunol Rev 249:218–238

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Lumeng CN, Saltiel AR (2011) Inflammatory links between obesity and metabolic disease. J Clin Invest 121:2111–2117

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Padwal R, Klarenbach S, Wiebe N, Birch D, Karmali S, Manns B, Hazel M, Sharma AM, Tonelli M (2011) Bariatric surgery: a systematic review and network meta-analysis of randomized trials. Obes Rev 12:602–621

    CAS  PubMed  Google Scholar 

  7. O’Brien PE, Hindle A, Brennan L, Skinner S, Burton P, Smith A, Crosthwaite G, Brown W (2019) Long-term outcomes after bariatric surgery: a systematic review and meta-analysis of weight loss at 10 or more years for all bariatric procedures and a single-centre review of 20-year outcomes after adjustable gastric banding. Obes Surg 29:3–14

    PubMed  Google Scholar 

  8. Magkos F, Fraterrigo G, Yoshino J, Luecking C, Kirbach K, Kelly SC, Las Fuentes L, He S, Okunade AL, Patterson BW, Samuel Klein S (2016) Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity. Cell Metab 23:591–601

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Hafida S, Mirshahi T, Nikolajczyk BS (2016) The impact of bariatric surgery on inflammation: quenching the fire of obesity? Curr Opin Endocrinol Diabetes Obes 23:373–378

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Cancello R, Zulian A, Gentilini D, Mencarelli M, Barba AD, Maffei M, Vitti P, Invitti C, Liuzzi A, Di Blasio AM (2013) Permanence of molecular features of obesity in subcutaneous adipose tissue of ex-obese subjects. Int J Obes 37:867–873

    CAS  Google Scholar 

  11. Caslin HL, Bhanot M, Bolus WR, Alyssa H, Hasty AH (2020) Adipose tissue macrophages: unique polarization and bioenergetics in obesity. Immunol Rev 295:101–113

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Cummings DE, Overduin J, Foster-Schubert KE (2004) Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. J Clin Endocrinol Metab 89:2608–2615

    CAS  PubMed  Google Scholar 

  13. Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C, Coupaye M, Pelloux V, Hugol D, Bouillot J-L, Bouloumié A, Barbatelli G, Cinti S, Svensson P-A, Barsh GS, Zucker J-D, Basdevant A, Langin D, Clément K (2005) Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 54:2277–2286

    CAS  Google Scholar 

  14. Aron-Wisnewsky J, Tordjman J, Poitou C, Darakhshan F, Hugol D, Basdevant A, Aissat A, Guerre-Millo M, Clément K (2009) Human adipose tissue macrophages: M1 and M2 cell surface markers in subcutaneous and omental depots and after weight loss. J Clin Endocrinol Metab 94:4619–4623

    CAS  PubMed  Google Scholar 

  15. Liu Y, Aron-Wisnewsky J, Marcelin G, Genser L, Le Naour G, Torcivia A, Bauvois B, Bouchet S, Pelloux V, Sasso M, Miette V, Tordjman J, Karine Clément K (2016) Accumulation and changes in composition of collagens in subcutaneous adipose tissue after bariatric surgery. J Clin Endocrinol Metab 101:293–304

    CAS  PubMed  Google Scholar 

  16. Martinez FO, Sica A, Mantovani A, Locati M (2008) Macrophage activation and polarization. Front Biosci 13:453–461. https://doi.org/10.2741/2692

    Article  CAS  PubMed  Google Scholar 

  17. Gordon S, Martinez FO (2010) Alternative activation of macrophages: mechanism and functions. Immunity 32:593–604

    CAS  PubMed  Google Scholar 

  18. Liu J, Divoux A, Sun J, Zhang J, Clément K, Glickman JN, Sukhova GK, Wolters PJ, Du J, Gorgun CZ, Doria A, Libby P, Blumberg RS, Kahn BB, Hotamisligil GS, Guo-Ping Shi G-P (2009) Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med 15:940–945

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Altintas MM, Azad A, Nayer B, Contreras G, Zaias J, Faul C, Reiser J, Ali Nayer A (2011) Mast cells, macrophages, and crown-like structures distinguish subcutaneous from visceral fat in mice. J Lipid Res 52:480–488

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Divoux A, Moutel S, Poitou C, Lacasa D, Veyrie N, Aissat A, Arock M, Guerre-Millo M, Clément K (2012) Mast cells in human adipose tissue: link with morbid obesity, inflammatory status, and diabetes. J Clin Endocrinol Metab 97:E1677–E1685. https://doi.org/10.1210/jc.2012-1532 (Epub 2012 Jun 28)

    Article  CAS  PubMed  Google Scholar 

  21. Botchkarev VA, Eichmüller S, Peters EM, Pietsch P, Johansson O, Maurer M, Paus R, R, (1997) A simple immunofluorescence technique for simultaneous visualization of mast cells and nerve fibers reveals selectivity and hair cycle-dependent changes in mast cell–nerve fiber contacts in murine Skin. Arch Dermatol Res 289:292–302

    CAS  PubMed  Google Scholar 

  22. Komi DEA, Wöhrl S, Bielory L (2020) Mast cell biology at molecular level: a comprehensive review. Clin Rev Allergy Immunol 58:342–365

    Google Scholar 

  23. Gri G, Frossi B, D’Inca F, Danelli L, Betto E, Mion F, Sibilano R, Pucillo C (2012) Mast cell: an emerging partner in immune interaction. Front Immunol 3:120. https://doi.org/10.3389/fimmu.2012.00120

    Article  PubMed  PubMed Central  Google Scholar 

  24. Voss M, Kotrba J, Gaffal E, Katsoulis-Dimitriou K, Dudec A (2021) Mast Cells in the skin: defenders of integrity or offenders in inflammation? Int J Mol Sci 22:4589. https://doi.org/10.3390/ijms22094589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Iddamalgoda A, Le QT, Ito K, Tanaka K, Kojima H, Hiroshi Kido H (2008) Mast cell tryptase and photoaging: possible involvement in the degradation of extra cellular matrix and basement membrane proteins. Arch Dermatol Res 300:S69–S76

    CAS  PubMed  Google Scholar 

  26. Di Girolamo N, Wakefield D (2000) In vitro and in vivo expression of interstitial collagenase/MMP-1 by human mast cells. Dev Immunol 7:131–142

    PubMed  PubMed Central  Google Scholar 

  27. Johnson JL, Jackson CL, Angelini GD, George SJ (1998) Activation of matrix-degrading metalloproteinases by mast cell proteases in atherosclerotic plaques. Arterioscler Thromb Vasc Biol 18:1707–1715

    CAS  PubMed  Google Scholar 

  28. Lijnen HR, Maquoi E, Holvoet P, Mertens A, Lupu F, Morange P, Alessi MC, Juhan-Vague I (2001) Adipose tissue expression of gelatinases in mouse models of obesity. Thromb Haemost 85:1111–1116

    CAS  PubMed  Google Scholar 

  29. Maquoi E, Munaut C, Colige A, Collen D, Lijnen HR (2002) Modulation of adipose tissue expression of murine matrix metalloproteinases and their tissue inhibitors with obesity. Diabetes 51:1093–1101

    CAS  PubMed  Google Scholar 

  30. Chavey C, Mari B, Monthouel M-N, Bonnafous S, Anglard P, Van Obberghen E, Tartare-Deckert S (2003) Matrix metalloproteinases are differentially expressed in adipose tissue during obesity and modulate adipocyte differentiation. J Biol Chem 278:11888–11896

    CAS  PubMed  Google Scholar 

  31. Bouloumie A, Sengenès C, Portolan G, Galitzky J, Lafontan M, M, (2001) Adipocyte produces matrix metalloproteinases 2 and 9: involvement in adipose differentiation. Diabetes 50:2080–2086

    CAS  PubMed  Google Scholar 

  32. Laimer M, Kaser S, Kranebitter M, Sandhofer A, Mühlmann G, Schwelberger H, Weiss H, Patsch JR, Ebenbichler CF (2005) Effect of pronounced weight loss on the nontraditional cardiovascular risk marker matrix metalloproteinase-9 in middle-aged morbidly obese women. Int J Obes 29:498–501

    CAS  Google Scholar 

  33. Ress C, Tschoner A, Ciardi C, Laimer MW, Engl JW, Sturm W, Weiss H, Tilg H, Ebenbichler CF, Patsch JR, Kaser S (2010) Influence of significant weight loss on serum matrix metalloproteinase (MMP)-7 levels. Eur Cytokine Netw 21:65–70

    CAS  PubMed  Google Scholar 

  34. Lee YJ, Heo Y-S, Park HS, Lee SH, Lee SK, Jang YJ (2014) Serum SPARC and matrix metalloproteinase-2 and metalloproteinase-9 concentrations after bariatric surgery in obese adults. Obes Surg 24:604–610

    PubMed  Google Scholar 

  35. Enser M, Avery NC (1984) Mechanical and chemical properties of the Skin and its collagen from lean and obese hyperglycaemic (ob/ob) mice. Diabetologia 27:44–49

    CAS  PubMed  Google Scholar 

  36. Ibuki A, Akase T, Nagase T, Minematsu T, Nakagami G, Horii M, Sagara H, Komeda T, Kobayashi M, Shimada T, Aburada M, Yoshimura K, Sugama J, Sanada H (2012) Skin fragility in obese diabetic mice: possible involvement of elevated oxidative stress and upregulation of matrix metalloproteinases. Exp Dermatol 21:178–183

    CAS  PubMed  Google Scholar 

  37. Catalan V, Gómez-Ambrosi J, Rodríguez A, Ramírez B, Silva C, Rotellar F, Gil MJ, Cienfuegos JA, Salvador J, Frühbeck G (2009) Increased adipose tissue expression of lipocalin-2 in obesity is related to inflammation and matrix metalloproteinase-2 and metalloproteinase-9 activities in humans. J Mol Med 8:803–813

    Google Scholar 

  38. Makihara H, Hidaka M, Sakai Y, Horie Y, Mitsui H, Ohashi K, Goshima Y, Akase T (2017) Reduction and fragmentation of elastic fibers in the Skin of obese mice is associated with altered mRNA expression levels of fibrillin-1 and neprilysin. Connect Tissue Res 58:479–486

    CAS  PubMed  Google Scholar 

  39. Prist IH, Salles AG, Lima TM, Modolin MLA, Gemperli R, Souza HP (2017) Extracellular matrix remodeling derangement in ex-obese patients. Mol Cell Biochem 425:1–7

    CAS  PubMed  Google Scholar 

  40. Brennan M, Bhatti H, Nerusu K, Bhagavathula N, Kang S, Fisher GJ, Varani J, Voorhees JJ (2003) Matrix metalloproteinase-1 is the major collagenolytic enzyme responsible for collagen damage in UV-irradiated human Skin. Photochem Photobiol 78:43–48

    CAS  PubMed  Google Scholar 

  41. Vaalamo M, Mattila L, Johansson N, Kariniemi AL, Karjalainen-Lindsberg ML, Kähäri VM, Saarialho-Kere U, U, (1997) Distinct populations of stromal cells express collagenase-3 (MMP-13) and collagenase-1(MMP-1) in chronic ulcers but not in normally healing wounds. J Invest Dermatol 109:96–101

    CAS  PubMed  Google Scholar 

  42. Solomonov I, Zehorai E, Talmi-Frank D, Wolf SG, Shainskaya A, Zhuravlev A, Kartvelishvily E, Visse R, Levin Y, Kampf N, Jaitin DA, David E, Amit I, Nagase H, Sagi I (2016) Distinct biological events generated by ECM proteolysis by two homologous collagenases. Proc Natl Acad Sci USA 113:10884–10889

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Ågren MS, Schnabel R, Christensen LH, Mirastschijski U (2015) Tumor necrosis factor-α-accelerated degradation of type I collagen in human Skin is associated with elevated matrix metalloproteinase (MMP)-1 and MMP-3 ex vivo. Eur J Cell Biol 94:12–21

    PubMed  PubMed Central  Google Scholar 

  44. Xie Y, Mustafa A, Yerzhan A, Merzhakupova D, Yerlan P, Orakov AN, AN, Wang X, Huang Y, Miao L, (2017) Nuclear matrix metalloproteinases: functions resemble the evolution from the intracellular to the extracellular compartment. Cell Death Discov. 3:17036. https://doi.org/10.1038/cddiscovery.2017.36

    Article  PubMed  PubMed Central  Google Scholar 

  45. Si-Tayeb K, Monvoisin A, Mazzocco C, Lepreux S, Decossas M, Cubel G, Taras D, Blanc J-F, Robinson DR, Rosenbaum J (2006) Matrix metalloproteinase 3 is present in the cell nucleus and is involved in apoptosis. Am J Pathol 169:1390–1401

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Limb GA, Matter K, Murphy G, Cambrey AD, Bishop PN, Morris GE, Khaw PT (2005) Matrix metalloproteinase-1 associates with intracellular organelles and confers resistance to lamin A/C degradation during apoptosis. Am J Pathol 166:1555–15563

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Sami K, Elshahat A, Moussa M, Abbas A, Amr Mahmoud A (2015) Image analyzer study of the skin in patients with morbid obesity and massive weight loss. Eplasty 15(e4):2015

    Google Scholar 

  48. Light D, Arvanitis GM, Abramson D, Glasberg SB (2010) Effect of weight loss after bariatric surgery on skin and the extracellular matrix. Plast Reconstr Surg 125:343–351

    CAS  PubMed  Google Scholar 

  49. Orpheu SC, Coltro PS, Scopel GP, Gomez DS, Rodrigues CJ, Modolin MLA, Faintuch J, Gemperli R, Ferreira MC (2010) Collagen and elastic content of abdominal skin after surgical weight loss. Obes Surg 20:480–486

    PubMed  Google Scholar 

  50. Rocha RI, Cintra Jr W, Modolin MLA, Takahashi GG, Elia TEG, Caldini ETEG, Gemperli https://pubmed.ncbi.nlm.nih.gov/33145720/—affiliation-3 R (2021). Skin changes due to massive weight loss: histological changes and the causes of the limited results of contouring surgeries. Obes Surg 31:1505–1513

  51. Veiga DF, Bussolaro RA, Kobayashi EY, Medeiros VP, Martins JRM, Garcia EB, Novo NF, Nader HB, Ferreira LM (2011) Glycosaminoglycans of abdominal skin after massive weight loss in post-bariatric female patients. Obes Surg 21:774–782

    PubMed  Google Scholar 

  52. Ezure T, Amano S (2009) Increased subcutaneous adipose tissue impairs dermal function in diet-induced obese mice. Exp Dermatol 19:878–882

    Google Scholar 

  53. Mori S, Shiraishi A, Epplen K, Butcher D, Murase D, Yasuda Y, Takatoshi Murase T (2017) Characterization of skin function associated with obesity and specific correlation to local/systemic parameters in American women. Lipids Health Dis 16:214. https://doi.org/10.1186/s12944-017-0608-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91

    CAS  PubMed  Google Scholar 

  55. Mihara M, Moriya Y, Ohsugi Y (1996) IL-6-soluble IL-6 receptor complex inhibits the proliferation of dermal fibroblasts. Int J Immunopharmacol 18:89–94

    CAS  PubMed  Google Scholar 

  56. Nettelhoff L, Grimm S, Jacobs C, Walter C, C, Pabst AM, Goldschmitt J, H Wehrbein H, (2016) Influence of mechanical compression on human periodontal ligament fibroblasts and osteoblasts. Clin Oral Investig 20:621–629

    CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Fundação de Amparo à Pesquisa para o SUS: gestão compartilhada. Grant Number: E-26/110.280/2014 (CMT)

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Authors and Affiliations

  1. Programa de Pós-Graduação em Ciências Cirúrgicas, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Carlo Amaral, João Paulo Verbicario & Christina Maeda Takiya

  2. Faculdade de Medicina, Universidade Federal do Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil

    Juliana Rodrigues da Costa & Matheus Oliveira Costa

  3. Dipartamento di Scienze Neurologiche e del Movimento, Sezione di Anatomia e Istologia della Universitádegli Studi di Verona, Verona, Italy

    Natale F. Gontijo-de-Amorim

  4. Programa de Pós-Graduação em Fisiopatologia e Ciências Cirúrgicas da Universidade Estadual do Rio de Janeiro, UERJ, Rio de Janeiro, Brazil

    Luiz Charles-de-Sá

  5. Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Christina Maeda Takiya

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  1. Carlo Amaral
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Correspondence to Luiz Charles-de-Sá.

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The study was approved by the Institutional Ethical and Research Committee Board under number 1,884,612 in January 2017. The study adhered to the ethical principles of the Declaration of Helsinki (2013).

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All procedures were performed with adequate understanding and written consent of the subjects.

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Amaral, C., da Costa, J.R., Costa, M.O. et al. M1 Polarized Macrophages Persist in Skin of Post-Bariatric Patients after 2 Years. Aesth Plast Surg 46, 287–296 (2022). https://doi.org/10.1007/s00266-021-02649-x

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