Skip to main content
SpringerLink
Log in

Weight loss is associated with improved endothelial dysfunction via NOX2-generated oxidative stress down-regulation in patients with the metabolic syndrome

  • IM - ORIGINAL
  • Published:
Internal and Emergency Medicine Aims and scope Submit manuscript

Abstract

The aim of this study was to assess whether adherence to a restricted-calorie, Mediterranean-type diet improves endothelial dysfunction and markers of oxidative stress in patients with metabolic syndrome. A moderately low-calorie (600 calories/day negative energy balance), low-fat, high-carbohydrate diet (<30% energy from fat, <10% from saturated fat and 55% from carbohydrate) was prescribed to 53 outpatients with the metabolic syndrome. Participants were divided into two groups according to body weight loss > or < 5% after 6 months. Group A (n = 23) showed a remarkable decrease in body weight (−6.8%), body-mass-index (−4.6%), waist circumference (−4.8%), HOMA-IR (−27.2%), plasma glucose, glycosylated haemoglobin, total and LDL-cholesterol, blood pressure, serum NOX2 (the catalytic core of NADPH oxidase) (−22.2%) and urinary8-isoprostanes (−39.0%) and an increase of serum NOx (Nitrite/Nitrate) (+116.8%) and adiponectine (+125.5%) as compared with those in group B (n = 30). A statistically significant increase in brachial artery flow-mediated dilatation was observed in group A (+24.7%; p < 0.001), while no changes were present in group B. Variations of flow-mediated dilatation were statistically and negatively correlated with changes of serum NOX2 levels (p = 0.04), body-mass-index (p < 0.01), waist circumference (0.01), glycosylated haemoglobin (p < 0.01), LDL-cholesterol (p < 0.01) and triglycerides (p < 0.05) and positively correlated with changes of serum NOx (p < 0.001) and adiponectin (p = 0.01). The results show that moderate weight loss is able to improve endothelial dysfunction in patients with the metabolic syndrome. The coexistent decrease of NOX2 activation suggests a role for oxidative stress in eliciting artery dysfunction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. (2001) Executive summary of the third report of the national cholesterol education program (NCEP) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) JAMA 285:2486–2497

  2. Despres JP, Lemieux I, Bergeron J et al (2008) Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol 28:1039–1049

    Article  PubMed  CAS  Google Scholar 

  3. Grundy SM (2008) Metabolic syndrome pandemic. Arterioscler Thromb Vasc Biol 28:629–636

    Article  PubMed  CAS  Google Scholar 

  4. Landmesser U, Drexler H (2005) The clinical significance of endothelial dysfunction. Curr Opin Cardiol 20: 547–-551

    Google Scholar 

  5. Corretti MC, Anderson TJ, Benjamin EJ et al (2002) Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the international brachial artery reactivity task force. J Am Coll Cardiol 39:257–265

    Article  PubMed  Google Scholar 

  6. Singh U, Jialal I (2006) Oxidative stress and atherosclerosis. Pathophysiology 13:129–142

    Article  PubMed  CAS  Google Scholar 

  7. Cangemi R, Angelico F, Loffredo L et al (2007) Oxidative stress-mediated arterial dysfunction in patients with metabolic syndrome: effect of ascorbic acid. Free Radic Biol Med 43:853–859

    Article  PubMed  CAS  Google Scholar 

  8. Hamburg NM, Larson MG, Vita JA et al (2008) Metabolic syndrome, insulin resistance, and brachial artery vasodilator function in Framingham Offspring participants without clinical evidence of cardiovascular disease. Am J Cardiol 101:82–88

    Article  PubMed  CAS  Google Scholar 

  9. Joannides R, Haefeli WE, Linder L et al (1995) Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation 91:1314–1319

    PubMed  CAS  Google Scholar 

  10. Cooke JP (2003) Flow, NO, and atherogenesis. Proc Natl Acad Sci USA 100:768–770

    Article  PubMed  CAS  Google Scholar 

  11. Heiss C, Lauer T, Dejam A et al (2006) Plasma nitroso compounds are decreased in patients with endothelial dysfunction. J Am Coll Cardiol 47:573–579

    Article  PubMed  CAS  Google Scholar 

  12. Loffredo L, Marcoccia A, Pignatelli P et al (2007) Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease. Eur Heart J 28:608–612

    Article  PubMed  CAS  Google Scholar 

  13. Cai H, Harrison DG (2000) Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 87:840–844

    PubMed  CAS  Google Scholar 

  14. Violi F, Marino R, Milite MT, Loffredo L (1999) Nitric oxide and its role in lipid peroxidation. Diabetes Metab Res Rev 15:283–288

    Article  PubMed  CAS  Google Scholar 

  15. Dai J, Jones DP, Goldberg J et al (2008) Association between adherence to the Mediterranean diet and oxidative stress. Am J Clin Nutr 88:1364–1370

    PubMed  CAS  Google Scholar 

  16. Rallidis LS, Lekakis J, Kolomvotsou A et al (2009) Close adherence to a Mediterranean diet improves endothelial function in subjects with abdominal obesity. Am J Clin Nutr 90:263–268

    Article  PubMed  CAS  Google Scholar 

  17. Forstermann U (2008) Oxidative stress in vascular disease: causes, defense mechanisms and potential therapies. Nat Clin Pract Cardiovasc Med 5:338–349

    Article  PubMed  Google Scholar 

  18. Bendall JK, Rinze R, Adlam D et al (2007) Endothelial Nox2 overexpression potentiates vascular oxidative stress and hemodynamic response to angiotensin II: studies in endothelial-targeted Nox2 transgenic mice. Circ Res 100:1016–1025

    Article  PubMed  CAS  Google Scholar 

  19. Oelze M, Warnholtz A, Faulhaber J et al (2006) NADPH oxidase accounts for enhanced superoxide production and impaired endothelium-dependent smooth muscle relaxation in BKbeta1-/- mice. Arterioscler Thromb Vasc Biol 26:1753–1759

    Article  PubMed  CAS  Google Scholar 

  20. Jung O, Schreiber JG, Geiger H, Pedrazzini T, Busse R, Brandes RP (2004) gp91phox-containing NADPH oxidase mediates endothelial dysfunction in renovascular hypertension. Circulation 109:1795–1801

    Article  PubMed  CAS  Google Scholar 

  21. Violi F, Sanguigni V, Carnevale R et al (2009) Hereditary deficiency of gp91(phox) is associated with enhanced arterial dilatation: results of a multicenter study. Circulation 120:1616–1622

    Article  PubMed  CAS  Google Scholar 

  22. Alberti KG, Zimmet P, Shaw J (2006) Metabolic syndrome-a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med 23:469–480

    Article  PubMed  CAS  Google Scholar 

  23. Wang Z, Ciabattoni G, Creminon C et al (1995) Immunological characterization of urinary 8-epi-prostaglandin F2 alpha excretion in man. J Pharmacol Exp Ther 275:94–100

    PubMed  CAS  Google Scholar 

  24. Pignatelli P, Carnevale R, Cangemi R et al (2010) Atorvastatin inhibits gp91phox circulating levels in patients with hypercholesterolemia. Arterioscler Thromb Vasc Biol 30:360–367

    Article  PubMed  CAS  Google Scholar 

  25. Fortuno A, Bidegain J, Robador PA et al (2009) Losartan metabolite EXP3179 blocks NADPH oxidase-mediated superoxide production by inhibiting protein kinase C: potential clinical implications in hypertension. Hypertension 54:744–750

    Article  PubMed  CAS  Google Scholar 

  26. Fito M, Guxens M, Corella D et al (2007) Effect of a traditional Mediterranean diet on lipoprotein oxidation: a randomized controlled trial. Arch Intern Med 167:1195–1203

    Article  PubMed  Google Scholar 

  27. Shai I, Schwarzfuchs D, Henkin Y et al (2008) Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med 359:229–241

    Article  PubMed  CAS  Google Scholar 

  28. Sacks FM, Bray GA, Carey VJ et al (2009) Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 360:859–873

    Article  PubMed  CAS  Google Scholar 

  29. Keogh JB, Brinkworth GD, Noakes M, Belobrajdic DP, Buckley JD, Clifton PM (2008) Effects of weight loss from a very-low-carbohydrate diet on endothelial function and markers of cardiovascular disease risk in subjects with abdominal obesity. Am J Clin Nutr 87:567–576

    PubMed  CAS  Google Scholar 

  30. Keogh JB, Brinkworth GD, Clifton PM (2007) Effects of weight loss on a low-carbohydrate diet on flow-mediated dilatation, adhesion molecules and adiponectin. Br J Nutr 98:852–859

    Article  PubMed  CAS  Google Scholar 

  31. Williams IL, Chowienczyk PJ, Wheatcroft SB et al (2005) Endothelial function and weight loss in obese humans. Obes Surg 15:1055–1060

    Article  PubMed  Google Scholar 

  32. Bigornia SJ, Mott MM, Hess DT et al (2010) Long-term successful weight loss improves vascular endothelial function in severely obese individuals. Obesity (Silver Spring) 18:754–759

    Article  Google Scholar 

  33. Davi G, Guagnano MT, Ciabattoni G et al (2002) Platelet activation in obese women: role of inflammation and oxidant stress. JAMA 288:2008–2014

    Article  PubMed  CAS  Google Scholar 

  34. Szabo C, Day BJ, Salzman AL (1996) Evaluation of the relative contribution of nitric oxide and peroxynitrite to the suppression of mitochondrial respiration in immunostimulated macrophages using a manganese mesoporphyrin superoxide dismutase mimetic and peroxynitrite scavenger. FEBS Lett 381:82–86

    Article  PubMed  CAS  Google Scholar 

  35. Carnevale R, Pignatelli P, Di Santo S et al (2010) Atorvastatin inhibits oxidative stress via adiponectin-mediated NADPH oxidase down-regulation in hypercholesterolemic patients. Atherosclerosis 213:225–234

    Article  PubMed  CAS  Google Scholar 

  36. Furukawa S, Fujita T, Shimabukuro M et al (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114:1752–1761

    PubMed  CAS  Google Scholar 

  37. Nakanishi S, Yamane K, Kamei N, Nojima H, Okubo M, Kohno N (2005) A protective effect of adiponectin against oxidative stress in Japanese Americans: the association between adiponectin or leptin and urinary isoprostane. Metabolism 54:194–199

    Article  PubMed  CAS  Google Scholar 

  38. Tao L, Gao E, Jiao X et al (2007) Adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress. Circulation 115:1408–1416

    Article  PubMed  CAS  Google Scholar 

  39. Shai I, Spence JD, Schwarzfuchs D et al (2010) Dietary intervention to reverse carotid atherosclerosis. Circulation 121:1200–1208

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We wish to thank nurses Monica Brancorsini and Daniela Salzano for their skilful cooperation.

Author Contributions: FA: wrote manuscript/study design; LL: performed statistical analysis and FMD measurements; PP: did study design and coordination; TA: did paper preparation/data elaboration; RC: did laboratory experimental procedures; AP, FA and IM: contributed to clinical data collection and elaboration; SD: performed laboratory experimental procedures; MD: reviewed and edited data; FV: did study design and paper preparation

Summary disclosure: The Authors have nothing to disclose

Conflict of interest

None.

Author information

Authors and Affiliations

  1. I Clinica Medica, Dipartimento di Medicina Interna e Specialità Mediche, La Sapienza Università di Roma, Policlinico Umberto I, Viale del Policlinico 155, 00161, Rome, Italy

    Francesco Angelico, Lorenzo Loffredo, Pasquale Pignatelli, Teresa Augelletti, Roberto Carnevale, Antonio Pacella, Fabiana Albanese, Ilaria Mancini, Serena Di Santo, Maria Del Ben & Francesco Violi

Authors
  1. Francesco Angelico
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lorenzo Loffredo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pasquale Pignatelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Teresa Augelletti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Roberto Carnevale
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Antonio Pacella
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fabiana Albanese
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ilaria Mancini
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Serena Di Santo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Maria Del Ben
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Francesco Violi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francesco Angelico.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Angelico, F., Loffredo, L., Pignatelli, P. et al. Weight loss is associated with improved endothelial dysfunction via NOX2-generated oxidative stress down-regulation in patients with the metabolic syndrome. Intern Emerg Med 7, 219–227 (2012). https://doi.org/10.1007/s11739-011-0591-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11739-011-0591-x

Keywords

Search

Navigation