Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Clinical Studies and Practice

Serum oxLDL–β2GPI complex reflects metabolic syndrome and inflammation in adipose tissue in obese

International Journal of Obesity volume 42, pages 405–411 (2018)Cite this article

Subjects

Abstract

Background/Objectives:

OxLDL–β2GPI complex has been suggested to have a role in the development of atherosclerosis and other inflammatory diseases. The aim of this study was to investigate the possible association of circulating oxLDL–β2GPI with obesity-induced inflammatory state of adipose tissue and related comorbidities as metabolic syndrome development.

Subjects/Methods:

Two cohorts of subjects were examined in the study. Cohort I: 36 women with wide range of body mass index (17–48 kg m−2) and metabolic status (with or without metabolic syndrome (MS); cohort II: 20 obese women undergoing a dietary intervention (DI) consisting of 1-month very-low-calorie diet, and 5 months of weight-stabilization period. Serum levels of oxLDL–β2GPI were measured by enzyme-linked immunosorbent assay. Insulin sensitivity was evaluated by hyperinsulinemic-euglycemic clamp and homeostasis model assessment of insulin resistance. mRNA expression of macrophage markers was determined in both subcutaneous (SAT) and visceral (VAT) adipose tissue in cohort I and in SAT in cohort II.

Results:

Serum oxLDL–β2GPI levels were increased in obese subjects with MS compared to lean or obese without MS (obese with MS: 26.6±5.0 vs lean: 15.17±1.97, P<0.001; vs obese without MS: 16.36±2.89, P<0.05). Serum oxLDL–β2GPI correlated with MS indices (glucose, high-density lipoprotein, triglyceride and ureic acid) and with mRNA expression of macrophage markers in VAT. Weight-reducing DI decreased serum oxLDL–β2GPI levels together with lipid parameters and the mRNA expression of inflammatory markers in SAT.

Conclusions:

OxLDL–β2GPI seems to be an important marker of visceral adipose tissue inflammation and possibly a factor contributing to insulin resistance and metabolic syndrome development in obese patients.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Daniele G, Guardado Mendoza R, Winnier D, Fiorentino TV, Pengou Z, Cornell J et al. The inflammatory status score including IL-6, TNF-alpha, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus. Acta Diabetol 2014; 51: 123–131.

    Article  CAS  Google Scholar 

  2. Osborn O, Olefsky JM . The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med 2012; 18: 363–374.

    Article  CAS  Google Scholar 

  3. Holvoet P, Mertens A, Verhamme P, Bogaerts K, Beyens G, Verhaeghe R et al. Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2001; 21: 844–848.

    Article  CAS  Google Scholar 

  4. Sanchez-Quesada JL, Vinagre I, De Juan-Franco E, Sanchez-Hernandez J, Bonet-Marques R, Blanco-Vaca F et al. Impact of the LDL subfraction phenotype on Lp-PLA2 distribution, LDL modification and HDL composition in type 2 diabetes. Cardiovasc Diabetol 2013; 12: 112.

    Article  CAS  Google Scholar 

  5. Aranda N, Fernandez-Cao JC, Tous M, Arija V . Increased iron levels and lipid peroxidation in a Mediterranean population of Spain. Eur J Clin Invest 2016; 46: 520–526.

    Article  CAS  Google Scholar 

  6. Frostegard J . Autoimmunity, oxidized LDL and cardiovascular disease. Autoimmun Rev 2002; 1: 233–237.

    Article  CAS  Google Scholar 

  7. Liu J, Rosner MH . Lipid abnormalities associated with end-stage renal disease. Semin Dial 2006; 19: 32–40.

    Article  Google Scholar 

  8. Mayr M, Kiechl S, Tsimikas S, Miller E, Sheldon J, Willeit J et al. Oxidized low-density lipoprotein autoantibodies, chronic infections, and carotid atherosclerosis in a population-based study. J Am Coll Cardiol 2006; 47: 2436–2443.

    Article  CAS  Google Scholar 

  9. Frostegard J, Haegerstrand A, Gidlund M, Nilsson J . Biologically modified LDL increases the adhesive properties of endothelial cells. Atherosclerosis 1991; 90: 119–126.

    Article  CAS  Google Scholar 

  10. Boullier A, Bird DA, Chang MK, Dennis EA, Friedman P, Gillotre-Taylor K et al. Scavenger receptors, oxidized LDL, and atherosclerosis. Ann N Y Acad Sci 2001; 947: 214–222 discussion 222-223.

    Article  CAS  Google Scholar 

  11. Hasunuma Y, Matsuura E, Makita Z, Katahira T, Nishi S, Koike T . Involvement of beta 2-glycoprotein I and anticardiolipin antibodies in oxidatively modified low-density lipoprotein uptake by macrophages. Clin Exp Immunol 1997; 107: 569–573.

    Article  CAS  Google Scholar 

  12. Kajiwara T, Yasuda T, Matsuura E . Intracellular trafficking of beta2-glycoprotein I complexes with lipid vesicles in macrophages: implications on the development of antiphospholipid syndrome. J Autoimmun 2007; 29: 164–173.

    Article  CAS  Google Scholar 

  13. George J, Harats D, Gilburd B, Afek A, Levy Y, Schneiderman J et al. Immunolocalization of beta2-glycoprotein I (apolipoprotein H) to human atherosclerotic plaques: potential implications for lesion progression. Circulation 1999; 99: 2227–2230.

    Article  CAS  Google Scholar 

  14. Greco TP, Conti-Kelly AM, Anthony JR, Greco Jr T, Doyle R, Boisen M et al. Oxidized-LDL/beta(2)-glycoprotein I complexes are associated with disease severity and increased risk for adverse outcomes in patients with acute coronary syndromes. Am J Clin Pathol 2010; 133: 737–743.

    Article  CAS  Google Scholar 

  15. Lopez LR, Hurley BL, Simpson DF, Matsuura E . Oxidized low-density lipoprotein/beta2-glycoprotein I complexes and autoantibodies in patients with type 2 diabetes mellitus. Ann N Y Acad Sci 2005; 1051: 97–103.

    Article  CAS  Google Scholar 

  16. Lopez LR, Simpson DF, Hurley BL, Matsuura E . OxLDL/beta2GPI complexes and autoantibodies in patients with systemic lupus erythematosus, systemic sclerosis, and antiphospholipid syndrome: pathogenic implications for vascular involvement. Ann N Y Acad Sci 2005; 1051: 313–322.

    Article  CAS  Google Scholar 

  17. Kraml PJ, Syrovatka P, Potockova J, Andel M . The oxidized low-density lipoprotein/beta2-glycoprotein I complex is associated with abdominal obesity in healthy middle-aged men. Ann Nutr Metab 2013; 62: 7–13.

    Article  CAS  Google Scholar 

  18. Arner P . Not all fat is alike. Lancet 1998; 351: 1301–1302.

    Article  CAS  Google Scholar 

  19. Merlotti C, Ceriani V, Morabito A, Pontiroli AE . Subcutaneous fat loss is greater than visceral fat loss with diet and exercise, weight-loss promoting drugs and bariatric surgery: a critical review and meta-analysis. Int J Obes (Lond) 2017; 41: 672–682.

    Article  CAS  Google Scholar 

  20. Montague CT, O'Rahilly S . The perils of portliness: causes and consequences of visceral adiposity. Diabetes 2000; 49: 883–888.

    Article  CAS  Google Scholar 

  21. Alberti KG, Zimmet P, Shaw J, Group IDFETFC. The metabolic syndrome—a new worldwide definition. Lancet 2005; 366: 1059–1062.

    Article  Google Scholar 

  22. Fujioka S, Matsuzawa Y, Tokunaga K, Tarui S . Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity. Metabolism 1987; 36: 54–59.

    Article  CAS  Google Scholar 

  23. DeFronzo RA, Tobin JD, Andres R . Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237: E214–E223.

    CAS  PubMed  Google Scholar 

  24. Rossmeislova L, Malisova L, Kracmerova J, Tencerova M, Kovacova Z, Koc M et al. Weight loss improves the adipogenic capacity of human preadipocytes and modulates their secretory profile. Diabetes 2013; 62: 1990–1995.

    Article  CAS  Google Scholar 

  25. Klimcakova E, Roussel B, Kovacova Z, Kovacikova M, Siklova-Vitkova M, Combes M et al. Macrophage gene expression is related to obesity and the metabolic syndrome in human subcutaneous fat as well as in visceral fat. Diabetologia 2011; 54: 876–887.

    Article  CAS  Google Scholar 

  26. Garg PK, McClelland RL, Jenny NS, Criqui MH, Greenland P, Rosenson RS et al. Lipoprotein-associated phospholipase A2 and risk of incident cardiovascular disease in a multi-ethnic cohort: the multi ethnic study of atherosclerosis. Atherosclerosis 2015; 241: 176–182.

    Article  CAS  Google Scholar 

  27. Liu J, Ren Y, Kang L, Zhang L . Oxidized low-density lipoprotein increases the proliferation and migration of human coronary artery smooth muscle cells through the upregulation of osteopontin. Int J Mol Med 2014; 33: 1341–1347.

    Article  CAS  Google Scholar 

  28. Mangge H, Zelzer S, Puerstner P, Schnedl WJ, Reeves G, Postolache TT et al. Uric acid best predicts metabolically unhealthy obesity with increased cardiovascular risk in youth and adults. Obesity (Silver Spring) 2013; 21: E71–E77.

    Article  CAS  Google Scholar 

  29. Berger JS, Rockman CB, Guyer KE, Lopez LR . Proatherogenic oxidized low-density lipoprotein/beta2-glycoprotein I complexes in arterial and venous disease. J Immunol Res 2014; 2014: 234316.

    Article  Google Scholar 

  30. Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N . Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract 2014; 105: 141–150.

    Article  CAS  Google Scholar 

  31. Boden G . Fatty acid-induced inflammation and insulin resistance in skeletal muscle and liver. Curr Diab Rep 2006; 6: 177–181.

    Article  CAS  Google Scholar 

  32. Zhang X, Xie Y, Zhou H, Xu Y, Liu J, Xie H et al. Involvement of TLR4 in oxidized LDL/beta2GPI/anti-beta2GPI-induced transformation of macrophages to foam cells. J Atheroscler Thromb 2014; 21: 1140–1151.

    Article  CAS  Google Scholar 

  33. Sies H, Berndt C, Jones DP . Oxidative stress. Annu Rev Biochem 2017; 86: 715–748.

    Article  CAS  Google Scholar 

  34. Anderson MT, Staal FJ, Gitler C, Herzenberg LA, Herzenberg LA . Separation of oxidant-initiated and redox-regulated steps in the NF-kappa B signal transduction pathway. Proc Natl Acad Sci USA 1994; 91: 11527–11531.

    Article  CAS  Google Scholar 

  35. Flohe L, Brigelius-Flohe R, Saliou C, Traber MG, Packer L . Redox regulation of NF-kappa B activation. Free Radic Biol Med 1997; 22: 1115–1126.

    Article  CAS  Google Scholar 

  36. Matsuura E, Lopez LR, Shoenfeld Y, Ames PR . beta2-glycoprotein I and oxidative inflammation in early atherogenesis: a progression from innate to adaptive immunity? Autoimmun Rev 2012; 12: 241–249.

    Article  CAS  Google Scholar 

  37. Kuwana M, Matsuura E, Kobayashi K, Okazaki Y, Kaburaki J, Ikeda Y et al. Binding of beta 2-glycoprotein I to anionic phospholipids facilitates processing and presentation of a cryptic epitope that activates pathogenic autoreactive T cells. Blood 2005; 105: 1552–1557.

    Article  CAS  Google Scholar 

  38. Amano SU, Cohen JL, Vangala P, Tencerova M, Nicoloro SM, Yawe JC et al. Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation. Cell Metab 2014; 19: 162–171.

    Article  CAS  Google Scholar 

  39. Kralova Lesna I, Kralova A, Cejkova S, Fronek J, Petras M, Sekerkova A et al. Characterisation and comparison of adipose tissue macrophages from human subcutaneous, visceral and perivascular adipose tissue. J Transl Med 2016; 14: 208.

    Article  Google Scholar 

  40. Kovacikova M, Sengenes C, Kovacova Z, Siklova-Vitkova M, Klimcakova E, Polak J et al. Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women. Int J Obes (Lond) 2011; 35: 91–98.

    Article  CAS  Google Scholar 

  41. Viardot A, Lord RV . Samaras K. The effects of weight loss and gastric banding on the innate and adaptive immune system in type 2 diabetes and prediabetes. J Clin Endocrinol Metab 2010; 95: 2845–2850.

    Article  CAS  Google Scholar 

  42. 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 

  43. Antunes BM, Rossi FE, Cholewa JM, Lira FS . Regular physical activity and vascular aging. Curr Pharm Des 2016; 22: 3715–3729.

    Article  CAS  Google Scholar 

  44. Lin N, Shi JJ, Li YM, Zhang XY, Chen Y, Calder PC et al. What is the impact of n-3 PUFAs on inflammation markers in type 2 diabetic mellitus populations?: a systematic review and meta-analysis of randomized controlled trials. Lipids Health Dis 2016; 15: 133.

    Article  Google Scholar 

Download references

Acknowledgements

The work was supported by grant 16-14048S from the Grant Agency of Czech Republic, and by Projects PRVOUK P31 and UNCE 20431 from Charles University in Prague.

Author information

Author notes

  1. Second Department of Internal Medicine, University Hospital Kralovske Vinohrady, Prague, Czech Republic

Authors and Affiliations

  1. Department for the Study of Obesity and Diabetes, Third Faculty of Medicine, Charles University, Prague, Czech Republic

    M Siklova, M Koc & L Rossmeislová

  2. Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague, and Institut des Maladies Métaboliques et Cardiovasculaires, Université Toulouse III Paul Sabatier, Toulouse, France

    M Siklova, M Koc, L Rossmeislová & P Kraml

Authors
  1. M Siklova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Koc
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L Rossmeislová
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P Kraml
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Siklova.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on International Journal of Obesity website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Siklova, M., Koc, M., Rossmeislová, L. et al. Serum oxLDL–β2GPI complex reflects metabolic syndrome and inflammation in adipose tissue in obese. Int J Obes 42, 405–411 (2018). https://doi.org/10.1038/ijo.2017.260

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2017.260

Search

Advanced search

Quick links