Serum Levels of Fetuin A and 8-hydroxydeoxyguanosine in Morbidly Obese Subjects

 

 Buy Article Permissions and Reprints

Abstract

Insulin resistance is one of the feature of obesity. Fetuin A is inhibitor of insulin receptor which belongs the family of receptor tyrosine kinase. It has been observed that fetuin-null mice are resistant to diet-induced obesity and they exhibit increased insulin sensitivity. Increased production of reactive oxygen species is suggested to be associated with insulin resistance. Attacks of reactive oxygen species to DNA results in base oxidation. Among the oxidized bases, 8-hydroxydeoxyguanosine is predominant lesion with pro-mutagenic potential. In the present study; measurement of serum levels of fetuin A and 8-hydroxydeoxyguanosine in obese subjects (n=46) and healthy controls (n=22), and examination of the relations between these parameters and insulin resistance have been purposed. Blood samples were taken form morbidly obese subjects after a 12 h fasting. Serum levels of fetuin A and 8-hydroxydeoxyguanosine were measured by ELISA. Statistical analysis was performed by Mann Whitney U test and correlations were examined by Spearman correlation coefficient. Serum levels of total cholesterol, HDL, LDL, VLDL, triglycerides, free T₃, free T₄, fasting glucose, c-peptide and %HbA1c in the obese group were found to be different from those in the control group. Serum level of fetuin A was found to be higher, 8-hydroxydeoxyguanosine level was found to be lower in the morbid obese group than those in the control group. Fetuin A was found to be positively correlated with HOMA-IR (r:0,40, P<0.05) and negatively correlated with 8-hydroxydeoxyguanosine (r:-0,52, P<0.01). No significant association was determined between body mass index and measured parameters. In conclusion, serum level of fetuin A is high in morbidly obese subjects and is negatively associated with 8-hydroxydeoxyguanosine level in peripheral circulation. Fetuin A may be a promising link between insulin resistance and obesity as well its comorbidities.

• References

• 1 Cominetti C, de Bortoli MC, Purgatto E et al. Associations between glutathione peroxidase-1 Pro198Leu polymorphism, selenium status, and DNA damage levels in obese women after consumption of Brazil nuts. Nutrition 2011; 27: 891-896
  CrossrefPubMedGoogle Scholar
• 2 Coppack SW. Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc 2001; 60: 349-356
  CrossrefPubMedGoogle Scholar
• 3 Joao Cabrera E, Valezi AC, Delfino VD et al. Reduction in plasma levels of inflammatory and oxidative stress indicators after Roux-en-Y gastric bypass. Obes Surg 2010; 20: 42-49
  CrossrefPubMedGoogle Scholar
• 4 Mori K, Emoto M, Yokoyama H et al. Association of serum fetuin-A with insulin resistance in type 2 diabetic and nondiabetic subjects. Diabetes care 2006; 29: 468
  CrossrefPubMedGoogle Scholar
• 5 Ix JH, Shlipak MG, Brandenburg VM et al. Association between human fetuin-A and the metabolic syndrome: data from the Heart and Soul Study. Circulation 2006; 113: 1760-1767
  CrossrefPubMedGoogle Scholar
• 6 Ix JH, Wassel CL, Bauer DC et al. Fetuin-A and BMD in older persons: the Health Aging and Body Composition (Health ABC) study. J Bone Miner Res 2009; 24: 514-521
  CrossrefPubMedGoogle Scholar
• 7 Stefan N, Fritsche A, Weikert C et al. Plasma fetuin-A levels and the risk of type 2 diabetes. Diabetes 2008; 57: 2762-2767
  CrossrefPubMedGoogle Scholar
• 8 Guzik TJ, Mussa S, Gastaldi D et al. Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation 2002; 105: 1656-1662
  CrossrefPubMedGoogle Scholar
• 9 Cooke MS, Evans MD, Dizdaroglu M et al. Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J 2003; 17: 1195-1214
  CrossrefPubMedGoogle Scholar
• 10 Furukawa S, Fujita T, Shimabukuro M et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004; 114: 1752-1761
  CrossrefPubMedGoogle Scholar
• 11 Keaney Jr. JF, Larson MG, Vasan RS et al. Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscler Thromb Vasc Biol 2003; 23: 434-439
  CrossrefPubMedGoogle Scholar
• 12 Matthews DR, Hosker JP, Rudenski AS et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
  Google Scholar
• 13 Robertson LA, Kim AJ, Werstuck GH. Mechanisms linking diabetes mellitus to the development of atherosclerosis: a role for endoplasmic reticulum stress and glycogen synthase kinase-3. Can J Physiol Pharmacol 2006; 84: 39-48
  CrossrefPubMedGoogle Scholar
• 14 Gumbs AA, Modlin IM, Ballantyne GH. Changes in insulin resistance following bariatric surgery: role of caloric restriction and weight loss. Obes Surg 2005; 15: 462-473
  CrossrefPubMedGoogle Scholar
• 15 Maiese K, Morhan SD, Chong ZZ. Oxidative stress biology and cell injury during type 1 and type 2 diabetes mellitus. Curr Neurovasc Res 2007; 4: 63-71
  CrossrefPubMedGoogle Scholar
• 16 Vincent HK, Taylor AG. Biomarkers and potential mechanisms of obesity-induced oxidant stress in humans. Int J Obes (Lond) 2006; 30: 400-418
  CrossrefPubMedGoogle Scholar
• 17 Randle PJ, Garland PB, Hales CN et al. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963; 1: 785-789
  PubMedGoogle Scholar
• 18 Maddux BA, See W, Lawrence Jr JC et al. Protection against oxidative stress-induced insulin resistance in rat L6 muscle cells by mircomolar concentrations of alpha-lipoic acid. Diabetes 2001; 50: 404-410
  CrossrefPubMedGoogle Scholar
• 19 Fridlyand LE, Philipson LH. Oxidative reactive species in cell injury: Mechanisms in diabetes mellitus and therapeutic approaches. Ann N Y Acad Sci 2005; 1066: 136-151
  CrossrefPubMedGoogle Scholar
• 20 Cardona F, Tunez I, Tasset I et al. Circulating antioxidant defences are decreased in healthy people after a high-fat meal. B J Nutr 2008; 100: 312-316
  PubMedGoogle Scholar
• 21 Sledzinski T, Goyke E, Smolenski RT et al. Decrease in serum protein carbonyl groups concentration and maintained hyperhomocysteinemia in patients undergoing bariatric surgery. Obes Surg 2009; 19: 321-326
  CrossrefPubMedGoogle Scholar
• 22 Uzun H, Konukoglu D, Gelisgen R et al. Plasma protein carbonyl and thiol stress before and after laparoscopic gastric banding in morbidly obese patients. Obes Surg 2007; 17: 1367-1373
  CrossrefPubMedGoogle Scholar
• 23 Tinahones FJ, Murri-Pierri M, Garrido-Sanchez L et al. Oxidative stress in severely obese persons is greater in those with insulin resistance. Obesity (Silver Spring) 2009; 17: 240-246
  CrossrefPubMedGoogle Scholar
• 24 Boesing F, Moreira EA, Wilhelm-Filho D et al. Roux-en-Y bypass gastroplasty: markers of oxidative stress 6 months after surgery. Obes Surg 2010; 20: 1236-1244
  CrossrefPubMedGoogle Scholar
• 25 Gao D, Wei C, Chen L et al. Oxidative DNA damage and DNA repair enzyme expression are inversely related in murine models of fatty liver disease. Am J Physiology Gastrointest Liver Physiol 2004; 287: G1070-G1077
  PubMedGoogle Scholar
• 26 Vartanian V, Lowell B, Minko IG et al. The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase. Proc Natl Acad Sci USA 2006; 103: 1864-1869
  CrossrefPubMedGoogle Scholar
• 27 Ix JH, Wassel CL, Chertow GM et al. Fetuin-A and change in body composition in older persons. J Clin Endocrinol Metab 2009; 94: 4492-4498
  CrossrefPubMedGoogle Scholar
• 28 Reinehr T, Roth CL. Fetuin-A and its relation to metabolic syndrome and fatty liver disease in obese children before and after weight loss. J Clin Endocrinol Metab 2008; 93: 4479-4485
  CrossrefPubMedGoogle Scholar
• 29 Brix JM, Stingl H, Hollerl F et al. Elevated Fetuin-A concentrations in morbid obesity decrease after dramatic weight loss. J Clin Endocrinol Metab 2010; 95: 4877-4881
  CrossrefPubMedGoogle Scholar