Advances in Clinical and Experimental Medicine

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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 4, April, p. 439–446

doi: 10.17219/acem/77982

Publication type: original article

Language: English

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Creative Commons BY-NC-ND 3.0 Open Access

Decreased serum level of nitric oxide in children with excessive body weight

Aleksandra Czumaj1,A,B,C,D,F, Marta Śledzińska2,B,E,F, Michał Brzeziński3,B,E,F, Agnieszka Szlagatys-Sidorkiewicz2,B,E,F, Ewa Słomińska4,C,E,F, Tomasz Śledziński1,A,D,E,F

1 Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Medical University of Gdańsk, Poland

2 Department of Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition, Faculty of Medicine, Medical University of Gdańsk, Poland

3 Department of Public Health and Social Medicine, Faculty of Health Sciences, Medical University of Gdańsk, Poland

4 Department of Biochemistry, Faculty of Medicine, Medical University of Gdańsk, Poland

Abstract

Background. Nitric oxide (NO) is an important mediator involved in vascular homeostasis. Changes in NO level are considered to be associated with obesity and its clinical consequences. Previous studies on NO levels in obese children provided inconclusive results, so this issue requires clarification.
Objectives. One of the main goals of this study was to assess whether childhood excessive body weight (EBW) is associated with changes in serum NO level and whether features like age and gender are linked to NO levels in selected groups.
Material and Methods. In the present study, the serum NO levels were compared in 43 children with EBW and 37 ageand gender-matched children with normal weight. Moreover, in both groups, body measurements and various clinical parameters, including the serum concentrations of arginine (Arg), a precursor of NO, were determined.
Results. The mean serum NO level in EBW group (8.7 ±3.1 μmol/L) was significantly lower than in normal weight group (22.2 ±11.5 μmol/L). However, the serum Arg concentrations were higher in EBW children than in controls. Serum asymmetric dimethylarginine (ADMA) levels were higher in EBW group and inversely correlated with serum NO. The EBW female subgroup was characterized by slightly lower level of NO than the EBW male subgroup. There were no significant changes in serum NO level among different age subgroups in both groups.
Conclusion. Our results revealed that EBW in children is associated with significantly decreased level of serum NO. The decreased serum NO level in EBW children is not a result of depleted Arg in the blood. Asymmetric dimethylarginine may at least partially contribute to decreased NO levels in children with EBW. A decreased level of NO could be a potential early marker of the risk of cardiovascular disorders developing in children with EBW.

Key words

children, overweight, cardiovascular risk, asymmetric dimethylarginine, nitric oxide

References (36)

  1. Toda N, Okamura T. Obesity impairs vasodilation and blood flow increase mediated by endothelial nitric oxide: An overview. J Clin Pharmacol. 2013;53(12):1228–1239.
  2. Must A, Strauss RS. Risk and consequences of childhood and adolescent obesity. Int J Obes Relat Metab Disord. 1999;23:2–11.
  3. Reilly JJ, Methven E, McDowell ZC, et al. Health consequences of obesity. Arch Dis Child. 2003;88(9):748–752.
  4. World Health Organization. Obesity: Preventing and managing the global epidemic. WHO Technical Report Series. 2000;894:16–60.
  5. European Environment and Health Information System. Prevalence of excess body weight and obesity in children and adolescents. Fact Sheet. 2007;2.3:1–4. http://www.euro.who.int/__data/assets/pdf_file/0005/96980/2.3.-Prevalence-of-overweight-and-obesity-EDITED_layouted_V3.pdf. Accessed December 15, 2016.
  6. Lundberg JO, Weitzberg E, Gladwin MT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov. 2008;7(2):156–167.
  7. Kleinert H, Pautz A, Linker K, Schwarz PM. Regulation of the expression of inducible nitric oxide synthase. Eur J Pharmacol. 2004;500(1–3):255–266.
  8. Elahi MM, Naseem KM, Matata BM. Nitric oxide in blood: The nitrosative-oxidative disequilibrium hypothesis on the pathogenesis of cardiovascular disease. FEBS J. 2007;274(4):906–923.
  9. Konukoglu D, Uzun H, Firtina S, Arica PC, Kocael A, Taskin M. Plasma adhesion and inflammation markers: Asymmetrical dimethyl-L-arginine and secretory phospholipase A2 concentrations before and after laparoscopic gastric banding in morbidly obese patients. Obes Surg. 2007;17(5):672–678.
  10. Pacher P, Beckman JS, Liaudet A. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007;87(1):315–424.
  11. Codoner-Franch P, Tavárez-Alonso S, Murria-Estal R, Megías-Vericat J, Tortajada-Girbés M, Alonso-Iglesias E. Nitric oxide production is increased in severely obese children and related to markers of oxidative stress and inflammation. Atherosclerosis. 2011;215(2):475–480.
  12. Gruber HJ, Mayer C, Fauler G, Granditis N, Wilders-Truschnig M. Obesity reduces the bioavailability of nitric oxide in juveniles. Int J Obes (Lond). 2008;32(5):826–831.
  13. Belo VA, Souza-Costa DC, Lacchini R, et al. Adiponectin associates positively with nitrite levels in children and adolescents. Int J Obes Relat Metab Disord. 2013;37:740–743.
  14. Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: International survey. BMJ. 2000;320(7244):240–1246.
  15. Granger DL, Taintor RR, Boockvar KS, Hibbs JB. Measurement of nitrate and nitrite in biological samples using nitrate reductase and Griess reaction. Methods Enzymol. 1996;268:142–151.
  16. Adrych K, Smoczyński M, Stojek M, et al. Decreased serum essential and aromatic amino acids in patients with chronic pancreatitis. World J Gastroenterol. 2010;16(35):4422–4427.
  17. Levy JC, Matthews DR, Hermans MP. Current homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 1998;21(12):2119–2192.
  18. Maniscalco M, de Laurentiis G, Zedda A, et al. Exhaled nitric oxide in severe obesity: Effect of weight loss. Respir Physiol Neurobiol. 2007; 156(3):370–373.
  19. Ghasemi A, Zahediasl S. Nitric oxide and clustering of metabolic syndrome components in pediatric. Eur J Epidemiol. 2010;25(1):45–53.
  20. Hrabák A, Derzbach L, Csuka I, Bajor T, Körner A. Role of nitric oxide (NO) metabolism and inflammatory mediators in childhood obesity. Inflamm Res. 2011;60(11):1061–1070.
  21. Furukawa S, Fujita T, Shimabukuro M, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004; 114(12):1752–1761.
  22. Colasanti M, Persichini T, Menegazzi M, et al. Induction of nitric oxide synthase mRNA expression: Suppression by exogenous nitric oxide. J Biol Chem. 1995;270(45):26731–26733.
  23. Park SK, Lin HL, Murphy S. Nitric oxide regulates nitric oxide synthase-2 gene expression by inhibiting NF-κB binding to DNA. Biochem J. 1997;322(Pt 2):609–613.
  24. Colasanti M, Suzuki H. The dual personality of NO. Trends Pharmacol Sci. 2000;21(7):249–252.
  25. Cancello R, Clément K. Is obesity an inflammatory illness? Role of low-grade inflammation and macrophage infiltration in human white adipose tissue. BJOG. 2006;113(10):1141–1147.
  26. Dandona P, Aljada A, Bandyopadhyay A. Inflammation: The link between insulin resistance, obesity and diabetes. Trends Immunol. 2004;25(1):1–4.
  27. Solorzano CM, McCartney CR. Obesity and pubertal transition in girls and boys. Reproduction. 2010;140(3):399–410.
  28. McDonald KK, Zharikov S, Block ER, Kilberg MS. A coveolar complex between the cationic amino acid transporter 1 and endothelial nitric-oxide synthase may explain the “arginine paradox”. J Biol Chem. 1997;272(50):31213–31216.
  29. Bode-Böger SM, Scalera F, Ignarro LJ. The L-arginine paradox: Importance of the L-arginine/asymmetrical dimethylarginine ratio. Pharmacol Ther. 2007;114(3):295–306.
  30. Dioguardi FS. To give or not to give? Lessons from the arginine paradox. J Nutrigenet Nutrigenomics. 2011;4(2):90–98.
  31. Shin S, Mohan S, Fung HL. Intracellular L-arginine concentration does not determine NO production in endothelial cells: Implications on the “L-arginine paradox”. Biochem Biophys Res Commun. 2011;414(4):660–663.
  32. Zani BG, Bohlen HG. Transport of extracellular L-arginine via cationic amino acid transporter is required during in vivo endothelial nitric oxide production. Am J Physiol Heart Circ Physiol. 2005;289(4):H1381–H1390.
  33. de Giorgis T, Marcovecchio ML, Giannini C, Chiavaroli V, Chiarelli F, Mohn AJ. Blood pressure from childhood to adolescence in obese youths in relation to insulin resistance and asymmetric dimethylarginine. J Endocrinol Invest. 2016;39:169–176.
  34. Śledziński T, Śledziński M, Smoleński RT, Swierczyński J. Increased serum nitric oxide concentration after bariatric surgery: A potential mechanism for cardiovascular benefit. Obes Surg. 2010;20(2):204–210.
  35. Sledzinska M, Liberek A, Kaminska B. Adipokines and obesity in children and adolescents [in Polish]. Med Wieku Rozwoj. 2009;13(4):244–251.
  36. Vasan RS. Biomarkers of cardiovascular disease: Molecular basis and practical considerations. Circulation. 2006;113(19):2335–2362.