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Neutrophil elastase and myeloperoxidase mRNA expression in overweight and obese subjects

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Abstract

Neutrophil elastase and myeloperoxidase enzymes have been implicated in high-fat diet-induced obesity, insulin resistance (IR) and atherosclerosis in animal models. The aim of the present study was to explore neutrophil elastase and myeloperoxidase mRNA expressions in the peripheral blood leukocytes (PBL) in overweight and obese subjects, and to correlate those mRNA expressions with BMI, IR and cardiovascular biomarkers. In this cross-sectional study, 74 apparently healthy subjects including 22 lean, 27 overweight and 25 obese subjects were recruited. Cardiovascular and metabolic biomarkers were evaluated from fasting blood samples. The mRNA levels of neutrophil elastase and myeloperoxidase genes in the PBL were quantified by real-time PCR. Compared to lean group, the overweight and obese groups showed significant upregulation of both neutrophil elastase (p < 0.001) and myeloperoxidase (p < 0.03) mRNA expressions in the PBL. But no difference was found between overweight and obese groups. The neutrophil elastase and myeloperoxidase mRNA levels showed significant positive correlation with BMI, serum triglyceride, atherogenic index of plasma and 10-year risk of developing cardiovascular disease. But no correlation was found with glucose, insulin or IR. It was concluded that the neutrophil elastase and myeloperoxidase genes are up-regulated in both overweight and obese subjects and are associated with BMI and markers of cardiovascular disease.

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References

  1. Caielli S, Banchereau J, Pascual V (2012) Neutrophils come of age in chronic inflammation. Curr Opin Immunol 24:671–677

    Article  CAS  Google Scholar 

  2. Pinegin B, Vorobjeva N, Pinegin V (2015) Neutrophil extracellular traps and their role in the development of chronic inflammation and autoimmunity. Autoimmun Rev 14:633–640

    Article  CAS  Google Scholar 

  3. Warnatsch A, Ioannou M, Wang Q, Papayannopoulos V (2015) Inflammation. Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis. Science 349:316–320

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  5. Talukdar S, Oh DY, Bandyopadhyay G et al (2012) Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med 18:1407–1412

    Article  CAS  Google Scholar 

  6. Kawanishi N, Niihara H, Mizokami T, Yada K, Suzuki K (2015) Exercise training attenuates neutrophil infiltration and elastase expression in adipose tissue of high-fat-diet-induced obese mice. Physiol Rep 3:e12534. https://doi.org/10.14814/phy2.12534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Michishita R, Shono N, Inoue T, Tsuruta T, Node K (2010) Effect of exercise therapy on monocyte and neutrophil counts in overweight women. Am J Med Sci 339:152–156

    Article  Google Scholar 

  8. Wang Q, Xie Z, Zhang W et al (2014) Myeloperoxidase deletion prevents high-fat diet-induced obesity and insulin resistance. Diabetes 63:4172–4185

    Article  CAS  Google Scholar 

  9. McMillen TS, Heinecke JW, LeBoeuf RC et al (2005) Expression of human myeloperoxidase by macrophages promotes atherosclerosis in mice. Circulation 111:2798–2804

    Article  CAS  Google Scholar 

  10. Mansuy-Aubert V, Zhou QL, Xie X et al (2013) Imbalance between neutrophil elastase and its inhibitor α1-antitrypsin in obesity alters insulin sensitivity, inflammation, and energy expenditure. Cell Metab 17:534–548

    Article  CAS  Google Scholar 

  11. Papayannopoulos V, Metzler KD, Hakkim A, Zychlinsky A (2010) Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J Cell Biol 191:677–691

    Article  CAS  Google Scholar 

  12. Nijhuis J, Rensen SS, Slaats Y, van Dielen FM, Buurman WA, Greve JW (2009) Neutrophil activation in morbid obesity, chronic activation of acute inflammation. Obesity 17:2014–2018

    Article  CAS  Google Scholar 

  13. Xu X, Su S, Wang X et al (2015) Obesity is associated with more activated neutrophils in African American male youth. Int J Obes 39:26–32

    Article  CAS  Google Scholar 

  14. Saab KR, Kendrick J, Yracheta JM, Lanaspa MA, Pollard M, Johnson RJ (2015) New insights on the risk for cardiovascular disease in African Americans: the role of added sugars. J Am Soc Nephrol 26:247–257

    Article  CAS  Google Scholar 

  15. WHO Expert Consultation (2004) Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 363:157–163

    Article  Google Scholar 

  16. Dobiásová M, Frohlich J (2001) The plasma parameter log [TG/HDL-C] as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma [FER[HDL]]. Clin Biochem 34:583–588

    Article  Google Scholar 

  17. D’Agostino RB Sr, Vasan RS, Pencina MJ et al (2008) General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation 117:743–753

    Article  Google Scholar 

  18. Pfaffl MW, Horgan GW, Dempfle L (2002) Relative expression software tool [REST] for group-wise comparison and statistical analysis of relative expression results in real time PCR. Nucleic Acids Res 30:e36

    Article  Google Scholar 

  19. Lavie CJ, Milani RV, Ventura HO (2009) Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss. J Am Coll Cardiol 53:1925–1932

    Article  Google Scholar 

  20. Afshin A, Forouzanfar MH, Reitsma MB et al (2017) Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med 377:13–27

    Article  Google Scholar 

  21. Gregor MF, Hotamisligil GS (2011) Inflammatory mechanisms in obesity. Annu Rev Immunol 29:415–445

    Article  CAS  Google Scholar 

  22. Nishimura S, Manabe I, Nagasaki M et al (2009) CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 15:914–920

    Article  CAS  Google Scholar 

  23. Hindle AK, Koury J, McCaffrey T, Fu SW, Brody F (2009) Dysregulation of gene expression within the peroxisome proliferator activated receptor pathway in morbidly obese patients. Surg Endosc 23:1292–1297

    Article  Google Scholar 

  24. Ghosh S, Dent R, Harper ME, Gorman SA, Stuart JS, McPherson R (2010) Gene expression profiling in whole blood identifies distinct biological pathways associated with obesity. BMC Med Genomics 3:56

    Article  Google Scholar 

  25. Wiersma JJ, Meuwese MC, van Miert JN et al (2008) Diabetes mellitus type 2 is associated with higher levels of myeloperoxidase. Med Sci Monit 14:CR406–CR410

    CAS  PubMed  Google Scholar 

  26. Gómez García A, Rivera Rodríguez M, Gómez Alonso C, Rodríguez Ochoa DY, Alvarez Aguilar C (2015) Myeloperoxidase is associated with insulin resistance and inflammation in overweight subjects with first-degree relatives with type2 diabetes mellitus. Diabetes Metab J 39:59–65

    Article  Google Scholar 

  27. Piwowar A, Knapik-Kordecka M, Warwas M (2000) Concentration of leukocyte elastase in plasma and polymorphonuclear neutrophil extracts in type 2 diabetes. Clin Chem Lab Med 38:1257–1261

    Article  CAS  Google Scholar 

  28. Fadini GP, Menegazzo L, Rigato M et al (2016) NETosis delays diabetic wound healing in mice and humans. Diabetes 65:1061–1071

    Article  CAS  Google Scholar 

  29. Wang Y, Xiao Y, Zhong L et al (2014) Increased neutrophil elastase and proteinase3 and augmented NETosis are closely associated with β-cell autoimmunity in patients with type 1 diabetes. Diabetes 63:4239–4248

    Article  CAS  Google Scholar 

  30. Sato N, Shimizu H, Suwa K, Shimomura Y, Kobayashi I, Mori M (1992) MPO activity and generation of active O2 species in leukocytes from poorly controlled diabetic patients. Diabetes Care 15:1050–1052

    Article  CAS  Google Scholar 

  31. Unubol M, Yavasoglu I, Kacar F et al (2015) Relationship between glycemic control and histochemical myeloperoxidase activity in neutrophils in patients with type2 diabetes. Diabetol Metab Syndr 7:119

    Article  Google Scholar 

  32. Qin J, Fu S, Speake C, Greenbaum CJ, Odegard JM (2016) NETosis-associated serum biomarkers are reduced in type1 diabetes in association with neutrophil count. Clin Exp Immunol 184:318–322

    Article  CAS  Google Scholar 

  33. Andrade VL, Petruceli E, Belo VA et al (2012) Evaluation of plasmatic MMP-8, MMP-9, TIMP-1 and MPO levels in obese and lean women. Clin Biochem 45:412–415

    Article  CAS  Google Scholar 

  34. Borato DC, Parabocz GC, Ribas JT et al (2016) Biomarkers in obesity: serum myeloperoxidase and traditional cardiac risk parameters. Exp Clin Endocrinol Diabetes 124:49–54

    Article  CAS  Google Scholar 

  35. Olza J, Aguilera CM, Gil-Campos M et al (2012) Myeloperoxidase is an early biomarker of inflammation and cardiovascular risk in prepubertal obese children. Diabetes Care 35:2373–2376

    Article  CAS  Google Scholar 

  36. Correia-Costa L, Sousa T, Morato M et al (2016) Association of myeloperoxidase levels with cardiometabolic factors and renal function in prepubertal children. Eur J Clin Invest 46:50–59

    Article  CAS  Google Scholar 

  37. Chhezom K, Arslan MI, Hoque MM, Biswas SK (2017) Biomarkers of cardiovascular and metabolic diseases in otherwise healthy overweight subjects in Bangladesh. Diabetes Metab Syndr 11:S381–S384

    Article  Google Scholar 

  38. Franssens BT, van der Graaf Y, Kappelle LJ et al (2015) Body weight, metabolic dysfunction, and risk of type 2 diabetes in patients at high risk for cardiovascular events or with manifest cardiovascular disease: a cohort study. Diabetes Care 38:1945–1951

    Article  CAS  Google Scholar 

  39. Funghetto SS, Silva Ade O, de Sousa NM et al (2015) Comparison of percentage body fat and body mass index for the prediction of inflammatory and atherogenic lipid risk profiles in elderly women. Clin Interv Aging 10:247–253

    Article  CAS  Google Scholar 

  40. Loprinzi PD, Crespo CJ, Andersen RE, Smit E (2015) Association of body mass index with cardiovascular disease biomarkers. Am J Prev Med 48:338–344

    Article  Google Scholar 

  41. Gómez-Ambrosi J, Silva C, Galofré JC et al (2012) Body mass index classification misses subjects with increased cardiometabolic risk factors related to elevated adiposity. Int J Obes (Lond) 36:286–294

    Article  Google Scholar 

  42. Guo X, Li Z, Guo L et al (2014) An update on overweight and obesity in rural Northeast China: from lifestyle risk factors to cardiometabolic comorbidities. BMC Public Health 14:1046

    Article  Google Scholar 

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Acknowledgements

This study was partly supported by the Higher Education Quality Enhancement Project (HEQEP CP-3073) of the University Grants Commission, Bangladesh; Bangladesh Medical Research Council (BMRC); and Unimed Limited. We would like to thank Dr. Md. Masum Alam, Kazi Tahsin Ahmed and Hosneara Akter for technical and administrative assistance.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka - 1000, Bangladesh

    Mohammad Ali, Shahana Jasmin, Sheikh M. K. Alam, M. I. Arslan & Subrata K. Biswas

  2. Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh

    Mohammad Fariduddin

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  1. Mohammad Ali
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  2. Shahana Jasmin
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Correspondence to Subrata K. Biswas.

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Ali, M., Jasmin, S., Fariduddin, M. et al. Neutrophil elastase and myeloperoxidase mRNA expression in overweight and obese subjects. Mol Biol Rep 45, 1245–1252 (2018). https://doi.org/10.1007/s11033-018-4279-4

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  • DOI: https://doi.org/10.1007/s11033-018-4279-4

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