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:

Obesity reduces the bioavailability of nitric oxide in juveniles

Abstract

Objective:

There is growing evidence that nitric oxide (NO) is critically involved in obesity and its clinical consequences like cardiovascular disease, hypertension and diabetes. We hypothesize that NO is already involved in the pathophysiology of juvenile obesity. We here determined the role of NO, its metabolites arginine and citrulline in obese and normal weight children.

Design:

We investigated 57 obese and 57 normal weight age- and gender-matched juveniles. Various clinical parameters as well as body measurements and intima media thickness were determined.

Results:

Obese juveniles revealed highly significant alterations in the NO pathway. NOX and citrulline were decreased in obese compared to normal weight juveniles and negatively correlated with body weight. Arginine was increased in obese juveniles and positively correlated with body weight. We found a significant negative correlation between NOX and oxidized low-density lipoprotein. Analysis of γ-aminobutyric acid (GABA) revealed correlations with the NO pathway as NOX and citrulline were negatively correlated with GABA and arginine showed a positive correlation.

Conclusion:

We show here that NO and its metabolites arginine and citrulline are already involved in juvenile obesity that may contribute to atherogenesis via reduced bioavailability of NO. Moreover, we identify GABA as a new parameter in the mechanism of obesity-related NO reduction.

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

Access options

Buy this article

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

Figure 1

Similar content being viewed by others

References

  1. 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: 906–923.

    Article  CAS  Google Scholar 

  2. Datta B, Tufnell-Barrett T, Bleasdale RA, Jones CJ, Beeton I, Paul V et al. Red blood cell nitric oxide as an endocrine vasoregulator: a potential role in congestive heart failure. Circulation 2004; 109: 1339–1342.

    Article  CAS  Google Scholar 

  3. Sobrevia L, Mann GE . Dysfunction of the endothelial nitric oxide signalling pathway in diabetes and hyperglycaemia. Exp Physiol 1997; 82: 423–452.

    Article  CAS  Google Scholar 

  4. Williams IL, Wheatcroft SB, Shah AM, Kearney MT . Obesity, atherosclerosis and the vascular endothelium: mechanisms of reduced nitric oxide bioavailability in obese humans. Int J Obes Relat Metab Disord 2002; 26: 754–764.

    Article  CAS  Google Scholar 

  5. Higashi Y, Sasaki S, Nakagawa K, Matsuura H, Chayama K, Oshima T . Effect of obesity on endothelium-dependent, nitric oxide-mediated vasodilation in normotensive individuals and patients with essential hypertension. Am J Hypertens 2001; 14: 1038–1045.

    Article  CAS  Google Scholar 

  6. Huang KT, Han TH, Hyduke DR, Vaughn MW, Van Herle H, Hein TW et al. Modulation of nitric oxide bioavailability by erythrocytes. Proc Natl Acad Sci USA 2001; 98: 11771–11776.

    Article  CAS  Google Scholar 

  7. Marfella R, Esposito K, Siniscalchi M, Cacciapuoti F, Giugliano F, Labriola D et al. Effect of weight loss on cardiac synchronization and proinflammatory cytokines in premenopausal obese women. Diabetes Care 2004; 27: 47–52.

    Article  CAS  Google Scholar 

  8. Pereira FO, Frode TS, Medeiros YS . Evaluation of tumour necrosis factor alpha, interleukin-2 soluble receptor, nitric oxide metabolites, and lipids as inflammatory markers in type 2 diabetes mellitus. Mediators Inflamm 2006; 2006: 39062.

    Article  Google Scholar 

  9. Ziccardi P, Nappo F, Giugliano G, Esposito K, Marfella R, Cioffi M et al. Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation 2002; 105: 804–809.

    Article  CAS  Google Scholar 

  10. Guzik TJ, Mangalat D, Korbut R . Adipocytokines—novel link between inflammation and vascular function? J Physiol Pharmacol 2006; 57: 505–528.

    CAS  Google Scholar 

  11. Konukoglu D, Serin O, Turhan MS . Plasma leptin and its relationship with lipid peroxidation and nitric oxide in obese female patients with or without hypertension. Arch Med Res 2006; 37: 602–606.

    Article  CAS  Google Scholar 

  12. Wilding JP . Leptin and the control of obesity. Curr Opin Pharmacol 2001; 1: 656–661.

    Article  CAS  Google Scholar 

  13. Konukoglu D, Serin O, Turhan MS . Plasma total homocysteine concentrations in obese and non-obese female patients with type 2 diabetes mellitus; its relations with plasma oxidative stress and nitric oxide levels. Clin Hemorheol Microcirc 2005; 33: 41–46.

    CAS  PubMed  Google Scholar 

  14. Chambers JC, McGregor A, Jean-Marie J, Obeid OA, Kooner JS . Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin C therapy. Circulation 1999; 99: 1156–1160.

    Article  CAS  Google Scholar 

  15. Backberg M, Meister B . Abnormal cholinergic and GABAergic vascular innervation in the hypothalamic arcuate nucleus of obese tub/tub mice. Synapse 2004; 52: 245–257.

    Article  Google Scholar 

  16. Stocker SD, Meador R, Adams JM . Neurons of the rostral ventrolateral medulla contribute to obesity-induced hypertension in rats. Hypertension 2007; 49: 640–646.

    Article  CAS  Google Scholar 

  17. Maniscalco M, de Laurentiis G, Zedda A, Faraone S, Giardiello C, Cristiano S et al. Exhaled nitric oxide in severe obesity: effect of weight loss. Respir Physiol Neurobiol 2007; 156: 370–373.

    Article  CAS  Google Scholar 

  18. Mather KJ, Lteif A, Steinberg HO, Baron AD . Interactions between endothelin and nitric oxide in the regulation of vascular tone in obesity and diabetes. Diabetes 2004; 53: 2060–2066.

    Article  CAS  Google Scholar 

  19. Naseem KM, Bruckdorfer KR . Hydrogen peroxide at low concentrations strongly enhances the inhibitory effect of nitric oxide on platelets. Biochem J 1995; 310 (Part 1): 149–153.

    Article  CAS  Google Scholar 

  20. Zou MH, Cohen R, Ullrich V . Peroxynitrite and vascular endothelial dysfunction in diabetes mellitus. Endothelium 2004; 11: 89–97.

    Article  CAS  Google Scholar 

  21. Forstermann U, Munzel T . Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation 2006; 113: 1708–1714.

    Article  Google Scholar 

  22. Vukosavljevic N, Jaron D, Barbee KA, Buerk DG . Quantifying the L-arginine paradox in vivo. Microvasc Res 2006; 71: 48–54.

    Article  CAS  Google Scholar 

  23. McDonald KK, Zharikov S, Block ER, Kilberg MS . A caveolar complex between the cationic amino acid transporter 1 and endothelial nitric-oxide synthase may explain the ‘arginine paradox’. J Biol Chem 1997; 272: 31213–31216.

    Article  CAS  Google Scholar 

  24. Reinehr T, Stoffel-Wagner B, Roth CL, Andler W . High-sensitive C-reactive protein, tumor necrosis factor alpha, and cardiovascular risk factors before and after weight loss in obese children. Metabolism 2005; 54: 1155–1161.

    Article  CAS  Google Scholar 

  25. Tsuda K, Nishio I . Leptin and nitric oxide production in normotensive and hypertensive men. Obes Res 2004; 12: 1223–1237.

    Article  CAS  Google Scholar 

  26. Lu HL, Wang HW, Wen Y, Zhang MX, Lin HH . Roles of adipocyte derived hormone adiponectin and resistin in insulin resistance of type 2 diabetes. World J Gastroenterol 2006; 12: 1747–1751.

    Article  CAS  Google Scholar 

  27. Silha JV, Krsek M, Skrha JV, Sucharda P, Nyomba BL, Murphy LJ . Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol 2003; 149: 331–335.

    Article  CAS  Google Scholar 

  28. Zou CC, Liang L, Hong F . Relationship between insulin resistance and serum levels of adiponectin and resistin with childhood obesity. Indian Pediatr 2007; 44: 275–279.

    PubMed  Google Scholar 

  29. Finkelstein JD . Pathways and regulation of homocysteine metabolism in mammals. Semin Thromb Hemost 2000; 26: 219–225.

    Article  CAS  Google Scholar 

  30. Yanfei W, Lin S, Junbao D, Chaoshu T . Impact of L-arginine on hydrogen sulfide/cystathionine-gamma-lyase pathway in rats with high blood flow-induced pulmonary hypertension. Biochem Biophys Res Commun 2006; 345: 851–857.

    Article  Google Scholar 

  31. Buck BJ, Kerman IA, Burghardt PR, Koch LG, Britton SL, Akil H et al. Upregulation of GAD65 mRNA in the medulla of the rat model of metabolic syndrome. Neurosci Lett 2007; 419: 178–183.

    Article  CAS  Google Scholar 

  32. Boesgaard TW, Castella SI, Andersen G, Albrechtsen A, Sparso T, Borch-Johnsen K et al. A-243A → G polymorphism upstream of the gene encoding GAD65 associates with lower levels of body mass index and glycaemia in a population-based sample of 5857 middle-aged White subjects. Diabet Med 2007; 24: 702–706.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We acknowledge the laboratory work of Mrs Sabine Pailer, Ms Kerstin Gerstl and Mr Fritz Wabnegger. This study was in part supported by grants of the ‘Zukunftsfonds Steiermark—Project 3003Med’ and the ‘Österreichisches Bundesministerium für Gesundheit, Familie und Jugend (BMGFJ)’.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H-J Gruber.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gruber, HJ., Mayer, C., Mangge, H. et al. Obesity reduces the bioavailability of nitric oxide in juveniles. Int J Obes 32, 826–831 (2008). https://doi.org/10.1038/sj.ijo.0803795

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0803795

Keywords

This article is cited by

Search

Quick links