Impact of Age and Metabolic Syndrome on the Adipokine Profile in Childhood and Adult Obesity

 

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Abstract

Objective: Obesity triggers an inflammatory response characterized by elevated circulating pro-inflammatory adipokines that predisposes to T2DM and cardiovascular disease. The objective of our study was to determine a potential association of adipokine plasma profile and the presence of a MetS in obese children and adolescents compared to adults.

Design and Methods: We determined serum levels of the adipokines soluble CD163 (sCD163), fetuin-A, osteopontin (OPN) and interleukin-1 receptor antagonist (IL-1 Ra) in 30 pediatric and 36 adult obese patients in a cross-sectional study.

Results: Serum concentrations of all tested adipokines except sCD163 were significantly elevated in the pediatric cohort compared to adults. Patients with MetS showed increased serum levels of sCD163, fetuin-A and IL-1 Ra levels compared to those without MetS. Fetuin-A and sCD163 remained significantly elevated by MetS within the juvenile group and borderline significant in the adults when tested separately. In the pediatric cohort we found correlations between sCD163 and fetuin-A as well as OPN and IL-1 Ra whereas correlations of sCD163 and both fetuin-A and IL-1 Ra were found in the adult group.

Conclusion: Our results indicate that adipokine profiles related to the presence of MetS significantly differ between pediatric and adult patients which may point to different underlying mechanisms.

^* DW and HM equally contributed to this manuscript.

• References

• 1 Alberti KG, Eckel RH, Grundy SM et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640-1645 DOI: 10.1161/CIRCULATIONAHA.109.192644.
  CrossrefPubMedGoogle Scholar
• 2 Olds T, Maher C, Zumin S et al. Evidence that the prevalence of childhood overweight is plateauing: data from nine countries. Int J Pediatr Obes 2011; 6: 342-360 DOI: 10.3109/17477166.2011.605895.
  CrossrefPubMedGoogle Scholar
• 3 Moran A, Jacobs Jr DR, Steinberger J et al. Changes in insulin resistance and cardiovascular risk during adolescence: establishment of differential risk in males and females. Circulation 2008; 117: 2361-2368 DOI: 10.1161/CIRCULATIONAHA.107.704569.
  CrossrefPubMedGoogle Scholar
• 4 Zimmet P, Alberti KG, Kaufman F et al. The metabolic syndrome in children and adolescents – an IDF consensus report. Pediatr Diabetes 2007; 8: 299-306 DOI: 10.1111/j.1399-5448.2007.00271.x.
  CrossrefPubMedGoogle Scholar
• 5 Ford ES, Li C, Zhao G et al. Prevalence of the metabolic syndrome among U.S. adolescents using the definition from the International Diabetes Federation. Diabetes Care 2008; 31: 587-589 DOI: 10.2337/dc07-1030.
  CrossrefPubMedGoogle Scholar
• 6 Sangun O, Dundar B, Kosker M et al. Prevalence of metabolic syndrome in obese children and adolescents using three different criteria and evaluation of risk factors. J Clin Res Pediatr Endocrinol 2011; 3: 70-76 DOI: 10.4274/jcrpe.v3i2.15.
  CrossrefPubMedGoogle Scholar
• 7 Daniels SR, Arnett DK, Eckel RH et al. Overweight in children and adolescents: pathophysiology, consequences, prevention, and treatment. Circulation 2005; 111: 1999-2012 DOI: 10.1161/01.CIR.0000161369.71722.10.
  CrossrefPubMedGoogle Scholar
• 8 Skinner AC, Steiner MJ, Henderson FW et al. Multiple markers of inflammation and weight status: cross-sectional analyses throughout childhood. Pediatrics 2010; 125: e801-e809 DOI: 10.1542/peds.2009-2182.
  CrossrefPubMedGoogle Scholar
• 9 Weisberg SP, McCann D, Desai M et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112: 1796-1808 DOI: 10.1172/JCI19246.
  CrossrefPubMedGoogle Scholar
• 10 Zeyda M, Stulnig TM. Adipose tissue macrophages. Immunol Lett 2007; 112: 61-67 DOI: 10.1016/j.imlet.2007.07.003.
  CrossrefPubMedGoogle Scholar
• 11 Mangge H, Almer G, Truschnig-Wilders M et al. Inflammation, adiponectin, obesity and cardiovascular risk. Curr Med Chem 2010; 17: 4511-4520
  CrossrefPubMedGoogle Scholar
• 12 Cook DG, Mendall MA, Whincup PH et al. C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors. Atherosclerosis 2000; 149: 139-150
  CrossrefPubMedGoogle Scholar
• 13 Kiefer FW, Zeyda M, Todoric J et al. Osteopontin expression in human and murine obesity: extensive local up-regulation in adipose tissue but minimal systemic alterations. Endocrinology 2008; 149: 1350-1357 DOI: 10.1210/en.2007-1312.
  CrossrefPubMedGoogle Scholar
• 14 Zeyda M, Gollinger K, Todoric J et al. Osteopontin is an activator of human adipose tissue macrophages and directly affects adipocyte function. Endocrinology 2011; 152: 2219-2227 DOI: 10.1210/en.2010-1328.
  CrossrefPubMedGoogle Scholar
• 15 Bertola A, Deveaux V, Bonnafous S et al. Elevated expression of osteopontin may be related to adipose tissue macrophage accumulation and liver steatosis in morbid obesity. Diabetes 2009; 58: 125-133 DOI: 10.2337/db08-0400.
  CrossrefPubMedGoogle Scholar
• 16 Kiefer FW, Zeyda M, Gollinger K et al. Neutralization of osteopontin inhibits obesity-induced inflammation and insulin resistance. Diabetes 2010; 59: 935-946 DOI: 10.2337/db09-0404.
  CrossrefPubMedGoogle Scholar
• 17 Sporrer D, Weber M, Wanninger J et al. Adiponectin downregulates CD163 whose cellular and soluble forms are elevated in obesity. Eur J Clin Invest 2009; 39: 671-679 DOI: 10.1111/j.1365-2362.2009.02170.x.
  CrossrefPubMedGoogle Scholar
• 18 Zeyda M, Farmer D, Todoric J et al. Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production. Int J Obes (Lond) 2007; 31: 1420-1428 DOI: 10.1038/sj.ijo.0803632.
  CrossrefPubMedGoogle Scholar
• 19 Zanni MV, Burdo TH, Makimura H et al. Relationship between monocyte/macrophage activation marker soluble CD163 and insulin resistance in obese and normal-weight subjects. Clin Endocrinol (Oxf) 2012; 77: 385-390 DOI: 10.1111/j.1365-2265.2011.04284.x.
  CrossrefPubMedGoogle Scholar
• 20 Juge-Aubry CE, Somm E, Giusti V et al. Adipose tissue is a major source of interleukin-1 receptor antagonist: upregulation in obesity and inflammation. Diabetes 2003; 52: 1104-1110
  CrossrefPubMedGoogle Scholar
• 21 Dinarello CA. The role of the interleukin-1-receptor antagonist in blocking inflammation mediated by interleukin-1. N Engl J Med 2000; 343: 732-734 DOI: 10.1056/NEJM200009073431011.
  CrossrefPubMedGoogle Scholar
• 22 Marculescu R, Endler G, Schillinger M et al. Interleukin-1 receptor antagonist genotype is associated with coronary atherosclerosis in patients with type 2 diabetes. Diabetes 2002; 51: 3582-3585
  CrossrefPubMedGoogle Scholar
• 23 Mathews ST, Singh GP, Ranalletta M et al. Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene. Diabetes 2002; 51: 2450-2458
  CrossrefPubMedGoogle Scholar
• 24 Srinivas PR, Wagner AS, Reddy LV et al. Serum alpha 2-HS-glycoprotein is an inhibitor of the human insulin receptor at the tyrosine kinase level. Mol Endocrinol 1993; 7: 1445-1455
  CrossrefPubMedGoogle Scholar
• 25 Cole TJ, Bellizzi MC, Flegal KM et al. Establishing a standard definition for child overweight and obesity worldwide: international survey. Bmj 2000; 320: 1240-1243
  CrossrefPubMedGoogle Scholar
• 26 Alberti KG, Zimmet P, Shaw J. Metabolic syndrome – a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med 2006; 23: 469-480 DOI: 10.1111/j.1464-5491.2006.01858.x.
  PubMedGoogle Scholar
• 27 Zimmet P, KG MMA, Serrano Rios M. A new international diabetes federation worldwide definition of the metabolic syndrome: the rationale and the results. Rev Esp Cardiol 2005; 58: 1371-1376
  CrossrefPubMedGoogle Scholar
• 28 Iwao S, Iwao N, Muller DC et al. Does waist circumference add to the predictive power of the body mass index for coronary risk?. Obes Res 2001; 9: 685-695 DOI: 10.1038/oby.2001.93.
  CrossrefPubMedGoogle Scholar
• 29 Parkner T, Sorensen LP, Nielsen AR et al. Soluble CD163: a biomarker linking macrophages and insulin resistance. Diabetologia 2012; 55: 1856-1862 DOI: 10.1007/s00125-012-2533-1.
  CrossrefPubMedGoogle Scholar
• 30 Simoni J, Simoni G, Griswold JA et al. Role of free hemoglobin in 8-iso prostaglandin F2-alpha synthesis in chronic renal failure and its impact on CD163-Hb scavenger receptor and on coronary artery endothelium. Asaio J 2006; 52: 652-661 DOI: 10.1097/01.mat.0000235282.89757.9f.
  CrossrefPubMedGoogle Scholar
• 31 Droste A, Sorg C, Hogger P. Shedding of CD163, a novel regulatory mechanism for a member of the scavenger receptor cysteine-rich family. Biochem Biophys Res Commun 1999; 256: 110-113 DOI: 10.1006/bbrc.1999.0294.
  CrossrefPubMedGoogle Scholar
• 32 Schaller G, Aso Y, Schernthaner GH et al. Increase of osteopontin plasma concentrations after bariatric surgery independent from inflammation and insulin resistance. Obes Surg 2009; 19: 351-356 DOI: 10.1007/s11695-008-9532-9.
  CrossrefPubMedGoogle Scholar
• 33 Riedl M, Vila G, Maier C et al. Plasma osteopontin increases after bariatric surgery and correlates with markers of bone turnover but not with insulin resistance. J Clin Endocrinol Metab 2008; 93: 2307-2312 DOI: 10.1210/jc.2007-2383.
  CrossrefPubMedGoogle Scholar
• 34 Marhaug G, Shah V, Shroff R et al. Age-dependent inhibition of ectopic calcification: a possible role for fetuin-A and osteopontin in patients with juvenile dermatomyositis with calcinosis. Rheumatology (Oxford) 2008; 47: 1031-1037 DOI: 10.1093/rheumatology/ken136.
  CrossrefPubMedGoogle Scholar
• 35 Mangge H, Freytag F, Almer G et al. Serum neopterin is not increased in obese juveniles. J Obes DOI: 10.1155/2011/946795.
  PubMedGoogle Scholar
• 36 Renkl AC, Wussler J, Ahrens T et al. Osteopontin functionally activates dendritic cells and induces their differentiation toward a Th1-polarizing phenotype. Blood 2005; 106: 946-955 DOI: 10.1182/blood-2004-08-3228.
  CrossrefPubMedGoogle Scholar
• 37 Saltevo J, Vanhala M, Kautiainen H et al. Levels of adiponectin, C-reactive protein and interleukin-1 receptor antagonist are associated with the relative change in body mass index between childhood and adulthood. Diab Vasc Dis Res 2007; 4: 328-331 DOI: 10.3132/dvdr.2007.060.
  CrossrefPubMedGoogle Scholar
• 38 Saltevo J, Laakso M, Jokelainen J et al. Levels of adiponectin, C-reactive protein and interleukin-1 receptor antagonist are associated with insulin sensitivity: a population-based study. Diabetes Metab Res Rev 2008; 24: 378-383 DOI: 10.1002/dmrr.831.
  CrossrefPubMedGoogle Scholar
• 39 Stelzer I, Zelzer S, Raggam RB et al. Link between leptin and interleukin-6 levels in the initial phase of obesity related inflammation. Transl Res 2012; 159: 118-124 DOI: 10.1016/j.trsl.2011.10.001.
  CrossrefPubMedGoogle Scholar
• 40 Weiss R, Dziura J, Burgert TS et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004; 350: 2362-2374 DOI: 10.1056/NEJMoa031049.
  CrossrefPubMedGoogle Scholar