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.

  • Review
  • Published:

Biomarkers and potential mechanisms of obesity-induced oxidant stress in humans

Abstract

Objective:

Oxidative stress may be the unifying mechanism underlying the development of comorbidities in obesity. Evidence suggests that a clustering of sources of oxidative stress exists in obesity: hyperglycemia, hyperleptinemia, increased tissue lipid levels, inadequate antioxidant defenses, increased rates of free radical formation, enzymatic sources within the endothelium, and chronic inflammation.

Method:

This review provides a summary of the available evidence on systemic oxidative stress in humans and specific metabolic pathways by which obesity may elevate systemic oxidant stress. The authors suggest possible methods of reducing oxidative stress such as antioxidant supplementation, caloric restriction and/or physical activity and surgical intervention to combat free radicals and reduce adipose tissue.

Results:

Obesity is associated with oxidative stress and can be reduced with weight loss (regardless of exercise or surgery induced weight loss), caloric restriction or antioxidant rich diets.

Conclusion:

Oxidative stress levels are elevated in human obesity, and these levels are modifiable with various lifestyle modifications and surgical interventions.

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
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Eckel RH . Obesity and heart disease: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 1997; 96: 3248–3250.

    Article  CAS  PubMed  Google Scholar 

  2. Wellman NS, Friedberg B . Causes and consequences of adult obesity: health, social and economic impacts in the United States. Asia Pac J Clin Nutr 2002; 11: S705–S709.

    Article  Google Scholar 

  3. Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM . Prevalence of overweight and obesity among US children, adolescents, and adults, 1999–2002. JAMA 2004; 291: 2847–2850.

    Article  CAS  PubMed  Google Scholar 

  4. Bray GA . Overweight, mortality and morbidity. In: Bouchard C (ed). Physical Activity and Obesity. Champaign, IL: Human Kinetics Publishers Inc., 2000, pp 31–54.

    Google Scholar 

  5. Davi G, Chiarelli F, Santilli F, Pomilio M, Vigneri S, Falco A et al. Enhanced lipid peroxidation and platelet activation in the early phase of type 1 diabetes mellitus: role of interleukin-6 and disease duration. Circulation 2003; 107: 3199–3203.

    Article  CAS  PubMed  Google Scholar 

  6. Higdon JV, Frei B . Obesity and oxidative stress: a direct link to CVD? Arterioscler Thromb Vasc Biol 2003; 23: 365–367.

    Article  CAS  PubMed  Google Scholar 

  7. Yu BP . Cellular defenses against damage from reactive oxygen species. Physiol Rev 1994; 74: 139–162.

    Article  CAS  PubMed  Google Scholar 

  8. Halliwell B, Whiteman M . Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br J Pharmacol 2004; 142: 231–255.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  10. Maritim AC, Sanders RA, Watkins III JB . Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 2003; 17: 24–38.

    Article  CAS  PubMed  Google Scholar 

  11. Ji LL . Exercise and oxidative stress: role of the cellular antioxidant systems. Exerc Sport Sci Rev 1995; 23: 135–166.

    Article  CAS  PubMed  Google Scholar 

  12. Kris-Etherton PM, Lichtenstein AH, Howard BV, Steinberg D, Witztum JL . Antioxidant vitamin supplements and cardiovascular disease. Circulation 2004; 110: 637–641.

    Article  CAS  PubMed  Google Scholar 

  13. Wei YH, Lu CY, Lee HC, Pang CY, Ma YS . Oxidative damage and mutation to mitochondrial DNA and age-dependent decline of mitochondrial respiratory function. Ann NY Acad Sci 1998; 854: 155–170.

    Article  CAS  PubMed  Google Scholar 

  14. Powers SK, Lennon SL, Quindry J, Mehta JL . Exercise and cardioprotection. Curr Opin Cardiol 2002; 17: 495–502.

    Article  PubMed  Google Scholar 

  15. Li HL, Liu DP, Liang CC . Paraoxonase gene polymorphisms, oxidative stress, and diseases. J Mol Med 2003; 81: 766–779.

    Article  CAS  PubMed  Google Scholar 

  16. Van Gaal LF, Vertommen J, De Leeuw IH . The in vitro oxidizability of lipoprotein particles in obese and non-obese subjects. Atherosclerosis 1998; 137: S39–S44.

    Article  CAS  PubMed  Google Scholar 

  17. Skrha J, Sindelka G, Kvasnicka J, Hilgertova J . Insulin action and fibrinolysis influenced by vitamin E in obese type 2 diabetes mellitus. Diabetes Res Clin Pract 1999; 44: 27–33.

    Article  CAS  PubMed  Google Scholar 

  18. Menon V, Ram M, Dorn J, Armstrong D, Muti P, Freudenheim JL et al. Oxidative stress and glucose levels in a population-based sample. Diabetic Med 2004; 21: 1346–1352.

    Article  CAS  PubMed  Google Scholar 

  19. Yue KK, Chung WS, Leung AW, Cheng CH . Redox changes precede the occurrence of oxidative stress in eyes and aorta, but not in kidneys of diabetic rats. Life Sci 2003; 73: 2557–2570.

    Article  CAS  PubMed  Google Scholar 

  20. Stojiljkovic MP, Lopes HF, Zhang D, Morrow JD, Goodfriend TL, Egan BM . Increasing plasma fatty acids elevates F2-isoprostanes in humans: implications for the cardiovascular risk factor cluster. J Hypertens 2002; 20: 1215–1221.

    Article  CAS  PubMed  Google Scholar 

  21. Myara I, Alamowitch C, Michel O, Heudes D, Bariety J, Guy-Grand B et al. Lipoprotein oxidation and plasma vitamin E in nondiabetic normotensive obese patients. Obes Res 2003; 11: 112–120.

    Article  CAS  PubMed  Google Scholar 

  22. Ozata M, Mergen M, Oktenli C, Aydin A, Sanisoglu SY, Bolu E et al. Increased oxidative stress and hypozincemia in male obesity. Clin Biochem 2002; 35: 627–631.

    Article  CAS  PubMed  Google Scholar 

  23. Olusi SO . Obesity is an independent risk factor for plasma lipid peroxidation and depletion of erythrocyte cytoprotectic enzymes in humans. Int J Obes Relat Metab Disord 2002; 26: 1159–1164.

    Article  CAS  PubMed  Google Scholar 

  24. Block G, Dietrich M, Norkus EP, Morrow JD, Hudes M, Caan B et al. Factors associated with oxidative stress in human populations. Am J Epidemiol 2002; 156: 274–285.

    Article  PubMed  Google Scholar 

  25. Keaney Jr JF, Larson MG, Vasan RS, Wilson PW, Lipinska I, Corey D et al. Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscler Thromb Vasc Biol 2003; 23: 434–439.

    Article  CAS  PubMed  Google Scholar 

  26. Davi G, Guagnano MT, Ciabattoni G, Basili S, Falco A, Marinopiccoli M et al. Platelet activation in obese women: role of inflammation and oxidant stress. JAMA 2002; 288: 2008–2014.

    Article  CAS  PubMed  Google Scholar 

  27. Lemieux I, Pascot A, Couillard C, Lamarche B, Tchernof A, Almeras N et al. Hypertriglyceridemic waist: a marker of the atherogenic metabolic triad (hyperinsulinemia; hyperapolipoprotein B; small, dense LDL) in men? Circulation 2000; 102: 179–184.

    CAS  PubMed  Google Scholar 

  28. Konukoglu D, Serin O, Ercan M, Turhan MS . Plasma homocysteine levels in obese and non-obese subjects with or without hypertension; its relationship with oxidative stress and copper. Clin Biochem 2003; 36: 405–408.

    Article  CAS  PubMed  Google Scholar 

  29. Urakawa H, Katsuki A, Sumida Y, Gabazza EC, Murashima S, Morioka K et al. Oxidative stress is associated with adiposity and insulin resistance in men. J Clin Endocrinol Metab 2003; 88: 4673–4676.

    Article  CAS  PubMed  Google Scholar 

  30. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004; 114: 1752–1761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Saiki S, Sato T, Kohzuki M, Kamimoto M, Yosida T . Changes in serum hypoxanthine levels by exercise in obese subjects. Metab: Clin Exp 2001; 50: 627–630.

    Article  CAS  Google Scholar 

  32. Vincent HK, Morgan JW, Vincent KR . Obesity exacerbates oxidative stress levels after acute exercise. Med Sci Sports Exerc 2004; 36: 772–779.

    Article  CAS  PubMed  Google Scholar 

  33. Vincent HK, Vincent KR, Bourguignon C, Braith RW . Obesity and post-exercise oxidative stress in older women. Med Sci Sports Exerc 2005; 37: 213–219.

    Article  CAS  PubMed  Google Scholar 

  34. Vincent HK, Bourguignon C, Frick KI, Rutkowksi JR, Vincent KR, Weltman AL et al. Contributing factors to post-exercise oxidative stress in obesity. Obes Res 2005; in review.

  35. Bailey DM, Young IS, McEneny J, Lawrenson L, Kim J, Barden J et al. Regulation of free radical outflow from an isolated muscle bed in exercising humans. Am J Physiol Heart Circ Physiol 2004; 287: H1689–H1699.

    Article  CAS  PubMed  Google Scholar 

  36. Dandona P, Mohanty P, Ghanim H, Aljada A, Browne R, Hamouda W et al. The suppressive effect of dietary restriction and weight loss in the obese on the generation of reactive oxygen species by leukocytes, lipid peroxidation, and protein carbonylation. J Clin Endocrinol Metab 2001; 86: 355–362.

    CAS  PubMed  Google Scholar 

  37. Gredilla R, Barja G . The role of oxidative stress in relation to caloric restriction and longevity. Endocrinology 2005; 146: 3713–3717.

    Article  CAS  PubMed  Google Scholar 

  38. Lambert AJ, Wang B, Merry BJ . Exogenous insulin can reverse the effects of caloric restriction on mitochondria. Biochem Biophys Res Commun 2004; 316: 1196–1201.

    Article  CAS  PubMed  Google Scholar 

  39. Beard CM, Barnard RJ, Robbins DC, Ordovas JM, Schaefer EJ . Effects of diet and exercise on qualitative and quantitative measures of LDL and its susceptibility to oxidation. Arterioscler Thromb Vasc Biol 1996; 16: 201–207.

    Article  CAS  PubMed  Google Scholar 

  40. Roberts CK, Vaziri ND, Barnard RJ . Effect of diet and exercise intervention on blood pressure, insulin, oxidative stress, and nitric oxide availability. Circulation 2002; 106: 2530–2532.

    Article  CAS  PubMed  Google Scholar 

  41. Lopes HF, Martin KL, Nashar K, Morrow JD, Goodfriend TL, Egan BM . DASH diet lowers blood pressure and lipid-induced oxidative stress in obesity. Hypertension 2003; 41: 422–430.

    Article  CAS  PubMed  Google Scholar 

  42. Chen G, Heilbrun LK, Venkatramanamoorthy R, Maranci V, Redd JN, Klurfeld DM et al. Effects of low-fat and/or high-fruit-and-vegetable diets on plasma levels of 8-isoprostane-F2alpha in the Nutrition and Breast Health Study. Nutr Cancer 2004; 50: 155–160.

    Article  CAS  PubMed  Google Scholar 

  43. Ozcelik O, Ozkan Y, Karatas K, Kelestimur H . Exercise training as an adjunct to Orlistat therapy reduces oxidative stress in obese subjects. Tohoku J Exp Med 2005; 206: 313–318.

    Article  CAS  PubMed  Google Scholar 

  44. Chang SP, Chen YH, Chang WC, Liu IM, Cheng JT . Increase of anti-oxidation by exercise in the liver of obese Zucker rats. Clin Exp Pharmacol Physiol 2004; 31: 506–511.

    Article  CAS  PubMed  Google Scholar 

  45. Saengsirisuwan V, Perez FR, Sloniger JA, Maier T, Henriksen EJ . Interactions of exercise training and alpha-lipoic acid on insulin signaling in skeletal muscle of obese Zucker rats. Am J Physiol Endocrinol Metab 2004; 287: E529–E536.

    Article  CAS  PubMed  Google Scholar 

  46. Yesilbursa D, Serdar Z, Serdar A, Sarac M, Coskun S, Jale C . Lipid peroxides in obese patients and effects of weight loss with Orlistat on lipid peroxides levels. Int J Obes Relat Metab Disord 2005; 29: 142–145.

    Article  CAS  Google Scholar 

  47. Kisakol G, Guney E, Bayraktar F, Yilmaz C, Kabalak T, Ozmen D . Effect of surgical weight loss on free radical and antioxidant balance: a preliminary report. Obes Surg 2002; 12: 795–800.

    Article  PubMed  Google Scholar 

  48. Uzun H, Zengin K, Taskin M, Aydin S, Simsek G, Dariyerli N . Changes in leptin, plasminogen activator factor and oxidative stress in morbidly obese patients following open and laparoscopic Swedish adjustable gastric banding. Obes Surg 2004; 14: 659–665.

    Article  PubMed  Google Scholar 

  49. Evans JL, Goldfine ID, Maddux BA, Grodsky GM . Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 2002; 23: 599–622.

    Article  CAS  PubMed  Google Scholar 

  50. Russell AP, Gastaldi G, Bobbioni-Harsch E, Arboit P, Gobelet C, Deriaz O et al. Lipid peroxidation in skeletal muscle of obese as compared to endurance-trained humans: a case of good vs bad lipids? FEBS Lett 2003; 551: 104–106.

    Article  CAS  PubMed  Google Scholar 

  51. Aronson D, Rayfield EJ . How hyperglycemia promotes atherosclerosis: molecular mechanisms. Cardiovasc Diabetol 2002; 1: 1–10.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Salvadori A, Fanari P, Fontana M, Buontempi L, Saezza A, Baudo S et al. Oxygen uptake and cardiac performance in obese and normal subjects during exercise. Respiration 1999; 66: 25–33.

    Article  CAS  PubMed  Google Scholar 

  53. Beltowski J, Wojcicka G, Gorny D, Marciniak A . The effect of dietary-induced obesity on lipid peroxidation, antioxidant enzymes and total plasma antioxidant capacity. J Physiol Pharmacol 2000; 51 (Part 2): 883–896.

    CAS  PubMed  Google Scholar 

  54. Vincent HK, Powers SK, Dirks AJ, Scarpace PJ . Mechanism for obesity-induced increase in myocardial lipid peroxidation. Int J Obes Relat Metab Disord 2001; 25: 378–388.

    Article  CAS  PubMed  Google Scholar 

  55. Ohrvall M, Tengblad S, Vessby B . Lower tocopherol serum levels in subjects with abdominal adiposity. J Intern Med 1993; 234: 53–60.

    Article  CAS  PubMed  Google Scholar 

  56. Moor de Burgos A, Wartanowicz M, Ziemlanski S . Blood vitamin and lipid levels in overweight and obese women. Eur J Clin Nutr 1992; 46: 803–808.

    CAS  PubMed  Google Scholar 

  57. Wallstrom P, Wirfalt E, Lahmann PH, Gullberg B, Janzon L, Berglund G . Serum concentrations of beta-carotene and alpha-tocopherol are associated with diet, smoking, and general and central adiposity. Am J Clin Nutr 2001; 73: 777–785.

    Article  CAS  PubMed  Google Scholar 

  58. Fernandez-Real JM, Broch M, Vendrell J, Ricart W . Insulin resistance, inflammation, and serum fatty acid composition. Diabetes Care 2003; 26: 1362–1368.

    Article  CAS  PubMed  Google Scholar 

  59. Saito I, Yonemasu K, Inami F . Association of body mass index, body fat, and weight gain with inflammation markers among rural residents in Japan. Circ J 2003; 67: 323–329.

    Article  PubMed  Google Scholar 

  60. Egan BM, Greene EL, Goodfriend TL . Insulin resistance and cardiovascular disease. Am J Hypertens 2001; 14: 116S–125S.

    Article  CAS  PubMed  Google Scholar 

  61. Wheatcroft SB, Williams IL, Shah AM, Kearney MT . Pathophysiological implications of insulin resistance on vascular endothelial function. Diabetic Med 2003; 20: 255–268.

    Article  CAS  PubMed  Google Scholar 

  62. Bouloumie A, Marumo T, Lafontan M, Busse R . Leptin induces oxidative stress in human endothelial cells. FASEB J 1999; 13: 1231–1238.

    Article  CAS  PubMed  Google Scholar 

  63. Rodriguez-Manas L, Angulo J, Vallejo S, Peiro C, Sanchez-Ferrer A, Cercas E et al. Early and intermediate Amadori glycosylation adducts, oxidative stress, and endothelial dysfunction in the streptozotocin-induced diabetic rats vasculature. Diabetologia 2003; 46: 556–566.

    Article  CAS  PubMed  Google Scholar 

  64. Zhang H, Schmeisser A, Garlichs CD, Plotze K, Damme U, Mugge A et al. Angiotensin II-induced superoxide anion generation in human vascular endothelial cells: role of membrane-bound NADH-/NADPH-oxidases. Cardiovasc Res 1999; 44: 215–222.

    Article  CAS  PubMed  Google Scholar 

  65. Talior I, Yarkoni M, Bashan N, Eldar-Finkelman H . Increased glucose uptake promotes oxidative stress and PKC-delta activation in adipocytes of obese, insulin-resistant mice. Am J Physiol Endocrinol Metab 2003; 285: E295–E302.

    Article  CAS  PubMed  Google Scholar 

  66. Sen CK . Oxidants and antioxidants in exercise. J Appl Physiol 1995; 79: 675–686.

    Article  CAS  PubMed  Google Scholar 

  67. Ji LL . Exercise, oxidative stress, and antioxidants. Am J Sports Med 1996; 24 (Suppl 6): S20–S24.

    Article  CAS  PubMed  Google Scholar 

  68. Vincent HK, Bourguignon C, Taylor AG . Relationship between the newly proposed dietary ‘Phytochemical Index’, obesity and oxidative stress in young healthy adults. Int J Obes Relat Metab Disord 2005; in review.

  69. Decsi T, Molnar D, Koletzko B . Reduced plasma concentrations of alpha-tocopherol and beta-carotene in obese boys. J Pediatr 1997; 130: 653–655.

    Article  CAS  PubMed  Google Scholar 

  70. Viroonudomphol D, Pongpaew P, Tungtrongchitr R, Changbumrung S, Tungtrongchitr A, Phonrat B et al. The relationships between anthropometric measurements, serum vitamin A and E concentrations and lipid profiles in overweight and obese subjects. Asia Pac J Clin Nutr 2003; 12: 73–79.

    CAS  PubMed  Google Scholar 

  71. Reitman A, Friedrich I, Ben-Amotz A, Levy Y . Low plasma antioxidants and normal plasma B vitamins and homocysteine in patients with severe obesity. Israel Med Assoc J 2002; 4: 590–593.

    CAS  Google Scholar 

  72. Strauss RS . Comparison of serum concentrations of alpha-tocopherol and beta-carotene in a cross-sectional sample of obese and nonobese children (NHANES III). National Health and Nutrition Examination Survey. J Pediatr 1999; 134: 160–165.

    Article  CAS  PubMed  Google Scholar 

  73. Kuno T, Hozumi M, Morinobu T, Murata T, Mingci Z, Tamai H . Antioxidant vitamin levels in plasma and low density lipoprotein of obese girls. Free Radical Res 1998; 28: 81–86.

    Article  CAS  Google Scholar 

  74. Fenkci V, Fenkci S, Yilmazer M, Serteser M . Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease. Fertil Steril 2003; 80: 123–127.

    Article  PubMed  Google Scholar 

  75. Molnar D, Decsi T, Koletzko B . Reduced antioxidant status in obese children with multimetabolic syndrome. Int J Obes Relat Metab Disord 2004; 28: 1197–1202.

    Article  CAS  PubMed  Google Scholar 

  76. Bakker SJ, RG I, Teerlink T, Westerhoff HV, Gans RO, Heine RJ . Cytosolic triglycerides and oxidative stress in central obesity: the missing link between excessive atherosclerosis, endothelial dysfunction, and beta-cell failure? Atherosclerosis 2000; 148: 17–21.

    Article  CAS  PubMed  Google Scholar 

  77. Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M et al. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 2000; 49: 1939–1945.

    Article  CAS  PubMed  Google Scholar 

  78. Rodriguez-Porcel M, Lerman LO, Holmes Jr DR, Richardson D, Napoli C, Lerman A . Chronic antioxidant supplementation attenuates nuclear factor-kappa B activation and preserves endothelial function in hypercholesterolemic pigs. Cardiovasc Res 2002; 53: 1010–1018.

    Article  CAS  PubMed  Google Scholar 

  79. Lyon CJ, Law RE, Hsueh WA . Minireview: adiposity, inflammation, and atherogenesis. Endocrinology 2003; 144: 2195–2200.

    Article  CAS  PubMed  Google Scholar 

  80. Dobrian AD, Davies MJ, Prewitt RL, Lauterio TJ . Development of hypertension in a rat model of diet-induced obesity. Hypertension 2000; 35: 1009–1015.

    Article  CAS  PubMed  Google Scholar 

  81. Basu S, Riserus U, Turpeinen A, Vessby B . Conjugated linoleic acid induces lipid peroxidation in men with abdominal obesity. Clin Sci 2000; 99: 511–516.

    Article  CAS  Google Scholar 

  82. Riserus U, Vessby B, Arnlov J, Basu S . Effects of cis-9,trans-11 conjugated linoleic acid supplementation on insulin sensitivity, lipid peroxidation, and proinflammatory markers in obese men. Am J Clin Nutr 2004; 80: 279–283.

    Article  CAS  PubMed  Google Scholar 

  83. Kopp HP, Kopp CW, Festa A, Krzyzanowska K, Kriwanek S, Minar E et al. Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vasc Biol 2003; 23: 1042–1047.

    Article  CAS  PubMed  Google Scholar 

  84. Weyer C, Yudkin JS, Stehouwer CD, Schalkwijk CG, Pratley RE, Tataranni PA . Humoral markers of inflammation and endothelial dysfunction in relation to adiposity and in vivo insulin action in Pima Indians. Atherosclerosis 2002; 161: 233–242.

    Article  CAS  PubMed  Google Scholar 

  85. Maachi M, Pieroni L, Bruckert E, Jardel C, Fellahi S, Hainque B et al. Systemic low-grade inflammation is related to both circulating and adipose tissue TNFalpha, leptin and IL-6 levels in obese women. Int J Obes Relat Metab Disord 2004; 28: 993–997.

    Article  CAS  PubMed  Google Scholar 

  86. Dandona P, Weinstock R, Thusu K, Abdel-Rahman E, Aljada A, Wadden T . Tumor necrosis factor-alpha in sera of obese patients: fall with weight loss. J Clin Endocrinol Metab 1998; 83: 2907–2910.

    CAS  PubMed  Google Scholar 

  87. Hotamisligil GS, Murray DL, Choy LN, Spiegelman BM . Tumor necrosis factor-a inhibits signaling from the insulin receptor. Proc Natl Acad Sci USA 1994; 91: 4854–4858.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Ridker PM, Hennekens CH, Buring JE, Rifai N . C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342: 836–843.

    Article  CAS  PubMed  Google Scholar 

  89. Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsuzawa Y, Chao CL et al. Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab 2001; 86: 3815–3819.

    Article  CAS  PubMed  Google Scholar 

  90. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 1999; 100: 2473–2476.

    Article  CAS  PubMed  Google Scholar 

  91. Tsunekawa T, Hayashi T, Suzuki Y, Matsui-Hirai H, Kano H, Fukatsu A et al. Plasma adiponectin plays an important role in improving insulin resistance with glimepiride in elderly type 2 diabetic subjects. Diabetes Care 2003; 26: 285–289.

    Article  CAS  PubMed  Google Scholar 

  92. Kullo IJ, Hensrud DD, Allison TG . Comparison of numbers of circulating blood monocytes in men grouped by body mass index (<25, 25 to <30, ⩾30). Am J Cardiol 2002; 89: 1441–1443.

    Article  PubMed  Google Scholar 

  93. Garg R, Kumbkarni Y, Aljada A, Mohanty P, Ghanim H, Hamouda W et al. Troglitazone reduces reactive oxygen species generation by leukocytes and lipid peroxidation and improves flow-mediated vasodilatation in obese subjects. Hypertension 2000; 36: 430–435.

    Article  CAS  PubMed  Google Scholar 

  94. Lipinski B . Pathophysiology of oxidative stress in diabetes mellitus. J Diabetes Compl 2001; 15: 203–210.

    Article  CAS  Google Scholar 

  95. Wellen KE, Hotamisligil GS . Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 2003; 112: 1785–1788.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Rajagopalan S, Kurz S, Munzel T, Tarpey M, Freeman BA, Griendling KK et al. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 1996; 97: 1916–1923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Kaminski KA, Bonda TA, Korecki J, Musial WJ . Oxidative stress and neutrophil activation – the two keystones of ischemia/reperfusion injury. Int J Cardiol 2002; 86: 41–59.

    Article  PubMed  Google Scholar 

  98. Munzel T, Li H, Mollnau H, Hink U, Matheis E, Hartmann M et al. Effects of long-term nitroglycerin treatment on endothelial nitric oxide synthase (NOS III) gene expression, NOS III-mediated superoxide production, and vascular NO bioavailability. Circ Res 2000; 86: E7–E12.

    Article  CAS  PubMed  Google Scholar 

  99. Schiffrin EL, Hypertension CIoHRMRGo. Beyond blood pressure: the endothelium and atherosclerosis progression. Am J Hypertens 2002; 15 (Part 2): 115S–122S.

    Article  CAS  PubMed  Google Scholar 

  100. Dandona P, Kumar V, Aljada A, Ghanim H, Syed T, Hofmayer D et al. Angiotensin II receptor blocker valsartan suppresses reactive oxygen species generation in leukocytes, nuclear factor-kappa B, in mononuclear cells of normal subjects: evidence of an antiinflammatory action. J Clin Endocrinol Metab 2003; 88: 4496–4501.

    Article  CAS  PubMed  Google Scholar 

  101. Brasier AR, Recinos III A, Eledrisi MS . Vascular inflammation and the renin-angiotensin system. Arterioscler Thromb Vasc Biol 2002; 22: 1257–1266.

    Article  CAS  PubMed  Google Scholar 

  102. Frisbee JC, Maier KG, Stepp DW . Oxidant stress-induced increase in myogenic activation of skeletal muscle resistance arteries in obese Zucker rats. Am J Physiol Heart Circ Physiol 2002; 283: H2160–H2168.

    Article  CAS  PubMed  Google Scholar 

  103. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334: 292–295.

    Article  CAS  PubMed  Google Scholar 

  104. Maingrette F, Renier G . Leptin increases lipoprotein lipase secretion by macrophages: involvement of oxidative stress and protein kinase C. Diabetes 2003; 52: 2121–2128.

    Article  CAS  PubMed  Google Scholar 

  105. Beltowski J, Wojcicka G, Jamroz A . Leptin decreases plasma paraoxonase 1 (PON1) activity and induces oxidative stress: the possible novel mechanism for proatherogenic effect of chronic hyperleptinemia. Atherosclerosis 2003; 170: 21–29.

    Article  CAS  PubMed  Google Scholar 

  106. Faggioni R, Feingold KR, Grunfeld C . Leptin regulation of the immune response and the immunodeficiency of malnutrition. FASEB J 2001; 15: 2565–2571.

    Article  CAS  PubMed  Google Scholar 

  107. O'Rourke L, Gronning LM, Yeaman SJ, Shepherd PR . Glucose-dependent regulation of cholesterol ester metabolism in macrophages by insulin and leptin. J Biol Chem 2002; 277: 42557–42562.

    Article  CAS  PubMed  Google Scholar 

  108. Ferretti G, Bacchetti T, Moroni C, Savino S, Liuzzi A, Balzola F et al. Paraoxonase activity in high-density lipoproteins: a comparison between healthy and obese females. J Clin Endocrinol Metab 2005; 90: 1728–1733.

    Article  CAS  PubMed  Google Scholar 

  109. Morris CD, Carson S . Routine vitamin supplementation to prevent cardiovascular disease: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2003; 139: 56–70.

    Article  CAS  PubMed  Google Scholar 

  110. Anderson JW, Gowri MS, Turner J, Nichols L, Diwadkar VA, Chow CK et al. Antioxidant supplementation effects on low-density lipoprotein oxidation for individuals with type 2 diabetes mellitus. J Am Coll Nutr 1999; 18: 451–461.

    Article  CAS  PubMed  Google Scholar 

  111. Roussel AM, Kerkeni A, Zouari N, Mahjoub S, Matheau JM, Anderson RA . Antioxidant effects of zinc supplementation in Tunisians with type 2 diabetes mellitus. J Am Coll Nutr 2003; 22: 316–321.

    Article  CAS  PubMed  Google Scholar 

  112. Manning PJ, Sutherland WH, Walker RJ, Williams SM, De Jong SA, Ryalls AR et al. Effect of high-dose vitamin E on insulin resistance and associated parameters in overweight subjects. Diabetes Care 2004; 27: 2166–2171.

    Article  CAS  PubMed  Google Scholar 

  113. Laight DW, Desai KM, Gopaul NK, Anggard EE, Carrier MJ . F2-isoprostane evidence of oxidant stress in the insulin resistant, obese Zucker rat: effects of vitamin E. Eur J Pharmacol 1999; 377: 89–92.

    Article  CAS  PubMed  Google Scholar 

  114. Blakely S, Herbert A, Collins M, Jenkins M, Mitchell G, Grundel E et al. Lutein interacts with ascorbic acid more frequently than with alpha-tocopherol to alter biomarkers of oxidative stress in female zucker obese rats. J Nutr 2003; 133: 2838–2844.

    Article  CAS  PubMed  Google Scholar 

  115. Lean ME, Noroozi M, Kelly I, Burns J, Talwar D, Sattar N et al. Dietary flavonols protect diabetic human lymphocytes against oxidative damage to DNA. Diabetes 1999; 48: 176–181.

    Article  CAS  PubMed  Google Scholar 

  116. Perticone F, Ceravolo R, Candigliota M, Ventura G, Iacopino S, Sinopoli F et al. Obesity and body fat distribution induce endothelial dysfunction by oxidative stress: protective effect of vitamin C. Diabetes 2001; 50: 159–165.

    Article  CAS  PubMed  Google Scholar 

  117. Brennan LA, Morris GM, Wasson GR, Hannigan BM, Barnett YA . The effect of vitamin C or vitamin E supplementation on basal and H2O2-induced DNA damage in human lymphocytes. Br J Nutr 2000; 84: 195–202.

    Article  CAS  PubMed  Google Scholar 

  118. Dusinska M, Kazimirova A, Barancokova M, Beno M, Smolkova B, Horska A et al. Nutritional supplementation with antioxidants decreases chromosomal damage in humans. Mutagenesis 2003; 18: 371–376.

    Article  CAS  PubMed  Google Scholar 

  119. Kim MS, Park JY, Namkoong C, Jang PG, Ryu JW, Song HS et al. Anti-obesity effects of alpha-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase. Nat Med 2004; 10: 727–733.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The preparation of this paper was supported, in part, by Grant Numbers T32-AT00052 and K30-AT-00060 from the National Center for Complementary and Alternative Medicine (NCCAM), and from the University of Virginia General Clinical Center Grant Number 5 M01 RR000847. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM or the National Institutes of Health. We thank Elizabeth Tournquist, MA, and Jewel Holmberg for their editorial expertise in finalizing this paper.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H K Vincent.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vincent, H., Taylor, A. Biomarkers and potential mechanisms of obesity-induced oxidant stress in humans. Int J Obes 30, 400–418 (2006). https://doi.org/10.1038/sj.ijo.0803177

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0803177

Keywords

This article is cited by

Search

Quick links