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Increased plasma isoprostane is associated with visceral fat, high molecular weight adiponectin, and metabolic complications in obese children

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Abstract

Oxidative stress is considered to be increased in obese subjects. However, the association of oxidative stress with visceral adiposity and adiponectin level is not fully understood in children. Forty-four obese Japanese children and adolescents, 28 boys and 16 girls, with median age of 9.9 years [5.2–13.8 years], and the 28 age-matched non-obese healthy controls, 15 boys and 13 girls, were enrolled in this study. The median BMI Z scores were +2.21 [1.31–4.38] for the obese subjects and −0.72 [−2.11–1.31] for the control. Plasma concentrations of 8-epi-prostaglandin \( {{\hbox{F}}_{2\alpha }} \) (isoprostane), a marker of oxidative stress, and adiponectin fractions were assayed using ELISA. 8-epi-PGF\( _{2\alpha } \) levels were significantly higher in the obese group (37.1 [4.7–112.7], median and the range) than in the control (11.5 [4.5–27.3]). In a univariate analysis, concentrations of 8-epi-PGF\( _{2\alpha } \) positively correlated with visceral adipose tissue area measured by computed tomography, waist circumference, serum triglycerides, alanine aminotransferase, insulin levels, and the homeostasis of minimal assessment of insulin resistance and inversely correlated with high-density-lipoprotein cholesterol and high-molecular weight (HMW) adiponectin. Total-, medium-, or low-molecular weight adiponectin fraction did not show a significant correlation with 8-epi-PGF\( _{2\alpha } \). Forty of 44 obese children had one or more metabolic complications. The 8-epi-PGF\( _{2\alpha } \) levels also elevated with increasing numbers of obesity-related complications. These results suggest that oxidative stress is enhanced in relation to visceral fat accumulation and decreasing HMW adiponectin level in childhood obesity. Oxidative stress may be associated with the development of obesity-related complications.

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Abbreviations

PG:

Prostaglandin

HOMA-R:

Homeostasis of minimal assessment of insulin resistance

MS:

Metabolic syndrome

HMW:

High molecular weight

MMW:

Medium molecular weight

LMW:

Low molecular weight

BMI:

Body mass index

VAT:

Visceral adipose tissue area

References

  1. Alberti KG, Zimmet P, Shaw J, IDF Epidemiology Task Force Consensus Group (2005) The metabolic syndrome—a new worldwide definition. Lancet 366:1059–1062

    Article  PubMed  Google Scholar 

  2. Asayama K, Dobashi K, Hayashibe H et al (2002) Threshold values of visceral fat measures and their anthropometric alternatives for metabolic derangement in Japanese obese boys. Int J Obes Relat Metab Disord 26:208–213

    Article  CAS  PubMed  Google Scholar 

  3. Asayama K, Hayashibe H, Dobashi K et al (2003) Decrease in serum adiponectin level due to obesity and visceral fat accumulation in children. Obes Res 11:1072–1079

    Article  CAS  PubMed  Google Scholar 

  4. Asayama K, Ozeki T, Sugihara S et al (2003) Criteria for medical intervention in obese children: a new definition of ‘obesity disease’ in Japanese children. Pediatr Int 45:642–646

    Article  PubMed  Google Scholar 

  5. Araki S, Dobashi K, Kubo K et al (2006) N-acetylcysteine attenuates TNF-alpha induced changes in secretion of interleukin-6, plasminogen activator inhibitor-1 and adiponectin from 3 T3-L1 adipocytes. Life Sci 79:2405–2412

    Article  CAS  PubMed  Google Scholar 

  6. Araki S, Dobashi K, Kubo K et al (2006) High molecular weight, rather than total, adiponectin levels better reflect metabolic abnormalities associated with childhood obesity. J Clin Endocrinol Metab 91:5113–5116

    Article  CAS  PubMed  Google Scholar 

  7. Bakker SJ, IJzerman RG, Teerlink T et al (2000) Cytosolic triglycerides and oxidative stress in central obesity: the missing link between excessive atherosclerosis, endothelial dysfunction, and beta-cell failure? Atherosclerosis 148:17–21

    Article  CAS  PubMed  Google Scholar 

  8. Couillard C, Ruel G, Archer WR et al (2005) Circulating levels of oxidative stress markers and endothelial adhesion molecules in men with abdominal obesity. J Clin Endocrinol Metab 90:6454–6459

    Article  CAS  PubMed  Google Scholar 

  9. Cracowski JL, Durand T, Bessard G (2002) Isoprostanes as a biomarker of lipid peroxidation in humans: physiology, pharmacology and clinical implications. Trends Pharmacol Sci 23:360–366, Review

    Article  CAS  PubMed  Google Scholar 

  10. Dandona P, Mohanty P, Ghanim H et al (2001) 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 86:355–362

    Article  CAS  PubMed  Google Scholar 

  11. Dandona P, Aljada A, Bandyopadhyay A (2004) Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol 25:4–7, Review

    Article  CAS  PubMed  Google Scholar 

  12. Desideri G, De Simone M, Iughetti L et al (2005) Early activation of vascular endothelial cells and platelets in obese children. J Clin Endocrinol Metab 90:3145–3152

    Article  CAS  PubMed  Google Scholar 

  13. Fujita K, Nishizawa H, Funahashi T et al (2006) Systemic oxidative stress is associated with visceral fat accumulation and the metabolic syndrome. Circ J 70:1437–1442

    Article  CAS  PubMed  Google Scholar 

  14. 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

    CAS  PubMed  Google Scholar 

  15. Giannini C, de Giorgis T, Scarinci A et al (2008) Obese related effects of inflammatory markers and insulin resistance on increased carotid intima media thickness in pre-pubertal children. Atherosclerosis 197:448–456

    Article  CAS  PubMed  Google Scholar 

  16. Gopaul NK, Anggard EE, Mallet AI et al (1995) Plasma 8-epi-PGF2 alpha levels are elevated in individuals with non-insulin dependent diabetes mellitus. FEBS Lett 368:225–229

    Article  CAS  PubMed  Google Scholar 

  17. Kadowaki T, Yamauchi T (2005) Adiponectin and adiponectin receptors. Endocr Rev 26:439–451

    Article  CAS  PubMed  Google Scholar 

  18. Kelly AS, Steinberger J, Kaiser DR et al (2006) Oxidative stress and adverse adipokine profile characterize the metabolic syndrome in children. J Cardiometab Syndr 1:248–252

    Article  PubMed  Google Scholar 

  19. Kelly AS, Steinberger J, Olson TP et al (2007) In the absence of weight loss, exercise training does not improve adipokines or oxidative stress in overweight children. Metabolism 56:1005–1009

    Article  CAS  PubMed  Google Scholar 

  20. Kumada M, Kihara S, Sumitsuji S, Osaka CAD Study Group et al (2003) Coronary artery disease Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 23:85–89

    Article  CAS  PubMed  Google Scholar 

  21. Maeda K, Okubo K, Shimomura I et al (1997) Analysis of an expression profile of genes in the human adipose tissue. Gene 190:227–235

    Article  CAS  PubMed  Google Scholar 

  22. Maeda K, Okubo K, Shimomura I et al (1996) cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem Biophys Res Commun 221:286–289

    Article  CAS  PubMed  Google Scholar 

  23. Martino F, Loffredo L, Carnevale R et al (2008) Oxidative stress is associated with arterial dysfunction and enhanced intima-media thickness in children with hypercholesterolemia: the potential role of nicotinamide-adenine dinucleotide phosphate oxidase. Pediatrics 122:e648–e655

    Article  PubMed  Google Scholar 

  24. Matsuzawa-Nagata N, Takamura T, Ando H et al (2008) Increased oxidative stress precedes the onset of high-fat diet-induced insulin resistance and obesity. Metabolism 57:1071–1077

    Article  CAS  PubMed  Google Scholar 

  25. Nakanishi S, Yamane K, Kamei N et al (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  CAS  PubMed  Google Scholar 

  26. Pou KM, Massaro JM, Hoffmann U et al (2007) Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress: the Framingham Heart Study. Circulation 116:1234–1241

    Article  CAS  PubMed  Google Scholar 

  27. Sinaiko AR, Steinberger J, Moran A et al (2005) Relation of body mass index and insulin resistance to cardiovascular risk factors, inflammatory factors, and oxidative stress during adolescence. Circulation 111:1985–1991

    Article  CAS  PubMed  Google Scholar 

  28. Schwedhelm E, Bartling A, Lenzen H et al (2004) Urinary 8-iso-prostaglandin F2alpha as a risk marker in patients with coronary heart disease: a matched case-control study. Circulation 109:843–848

    Article  CAS  PubMed  Google Scholar 

  29. Urakawa H, Katsuki A, Sumida Y et al (2003) Oxidative stress is associated with adiposity and insulin resistance in men. J Clin Endocrinol Metab 88:4673–4676

    Article  CAS  PubMed  Google Scholar 

  30. Waki H, Yamauchi T, Kamon J et al (2003) Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem 278:40352–4036

    Article  CAS  PubMed  Google Scholar 

  31. Weisberg SP, McCann D, Desai M et al (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808

    CAS  PubMed  Google Scholar 

  32. Xu H, Barnes GT, Yang Q et al (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830

    CAS  PubMed  Google Scholar 

  33. Yang S, Zhu H, Li Y et al (2000) Mitochondrial adaptations to obesity-related oxidant stress. Arch Biochem Biophys 378:259–268

    Article  CAS  PubMed  Google Scholar 

  34. Yoshida T, Kaneshi T, Shimabukuro T et al (2006) Serum C-reactive protein and its relation to cardiovascular risk factors and adipocytokines in Japanese children. J Clin Endocrinol Metab 91:2133–2137

    Article  CAS  PubMed  Google Scholar 

  35. Zimmet P, Alberti G, Kaufman F, International Diabetes Federation Task Force on Epidemiology and Prevention of Diabetes et al (2007) The metabolic syndrome in children and adolescents. Lancet 369:2059–2061

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank Miss Yuki Ohga for her technical assistance. This work was supported in part by a Grant-in-Aid for Scientific Research #21591340 and #18591173 from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

The authors declared no conflict of interest.

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Correspondence to Shunsuke Araki.

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Araki, S., Dobashi, K., Yamamoto, Y. et al. Increased plasma isoprostane is associated with visceral fat, high molecular weight adiponectin, and metabolic complications in obese children. Eur J Pediatr 169, 965–970 (2010). https://doi.org/10.1007/s00431-010-1157-z

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  • DOI: https://doi.org/10.1007/s00431-010-1157-z

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