Pediatric Gastroenterology, Hepatology & Nutrition

The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition (대한소아소화기영양학회)
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Role of Soluble Adiponectin Receptor 2 in Non-Alcoholic Fatty Liver Disease in Children

  • Aksoy, Gulsah Kaya (Department of Pediatrics, Akdeniz University Medical Faculty) ;
  • Artan, Reha (Department of Pediatric Gastroenterology, Akdeniz University Medical Faculty) ;
  • Aksoy, Cihat (Department of Radiology, Akdeniz University Medical Faculty) ;
  • Ozdem, Sebahat (Department of Biochemistry, Akdeniz University Medical Faculty) ;
  • Atalay, Atike (Department of Pediatric Gastroenterology, Akdeniz University Medical Faculty) ;
  • Yilmaz, Aygen (Department of Pediatric Gastroenterology, Akdeniz University Medical Faculty)
  • Received : 2018.11.30
  • Accepted : 2019.02.07
  • Published : 2019.09.15
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Abstract

Purpose: The incidence of non-alcoholic fatty liver disease (NAFLD) in children is gradually increasing. The aim of this study was to investigate the use of serum adiponectin and soluble adiponectin receptor 2 (soluble Adipo R2) levels for the diagnosis of fatty liver disease in obese and overweight children. Methods: The study included 51 obese and overweight children between the ages of 6 and 18 years diagnosed with NAFLD using ultrasonography and 20 children without fatty liver disease. Patients whose alanine transaminase level was two times higher than normal (${\geq}80U/L$) were included in the non-alcoholic steatohepatitis (NASH) group. Results: NASH was observed in 11 (21.6%) of the patients with NAFLD. The incidence of obesity was higher in patients with NASH (80% and 45%, p=0.021). While the adiponectin levels were similar in patients with NAFLD and those without, they were below the normal level in the whole study group. Adiponectin and soluble Adipo R2 levels of patients with NASH were lower than those in patients without NASH; however, this difference was not statistically significant (p=0.064 and p=0.463). Soluble Adipo R2 levels in obese patients with NAFLD were higher than those in obese children without NAFLD (p<0.001). Conclusion: Soluble adiponectin receptor 2 level is a noninvasive marker that can be used for the diagnosis of NAFLD in obese children.

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References

  1. Lavine JE, Schwimmer JB. Nonalcoholic fatty liver disease in the pediatric population. Clin Liver Dis 2004;8:549-58, viii-ix. https://doi.org/10.1016/j.cld.2004.04.010
  2. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221-31. https://doi.org/10.1056/NEJMra011775
  3. Roberts EA. Pediatric nonalcoholic fatty liver disease (NAFLD): a "growing" problem? J Hepatol 2007;46:1133-42. https://doi.org/10.1016/j.jhep.2007.03.003
  4. Clemente MG, Mandato C, Poeta M, Vajro P. Pediatric non-alcoholic fatty liver disease: recent solutions, unresolved issues, and future research directions. World J Gastroenterol 2016;22:8078-93. https://doi.org/10.3748/wjg.v22.i36.8078
  5. Anderson EL, Howe LD, Jones HE, Higgins JP, Lawlor DA, Fraser A. The prevalence of non-alcoholic fatty liver disease in children and adolescents: a systematic review and meta-analysis. PLoS One 2015;10:e0140908. https://doi.org/10.1371/journal.pone.0140908
  6. Day CP, James OF. Steatohepatitis: a tale of two "hits"? Gastroenterology 1998;114:842-5. https://doi.org/10.1016/S0016-5085(98)70599-2
  7. Teli MR, James OF, Burt AD, Bennett MK, Day CP. The natural history of nonalcoholic fatty liver: a followup study. Hepatology 1995;22:1714-9. https://doi.org/10.1002/hep.1840220616
  8. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001;7:941-6. https://doi.org/10.1038/90984
  9. Berg AH, Combs TP, Du X, Brownlee M, Scherer PE. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 2001;7:947-53. https://doi.org/10.1038/90992
  10. Fang X, Sweeney G. Mechanisms regulating energy metabolism by adiponectin in obesity and diabetes. Biochem Soc Trans 2006;34(Pt 5):798-801. https://doi.org/10.1042/BST0340798
  11. Pugia MJ, Franke DDH, Barnes SL, Zercher A, Brock D, Foltz M, et al. Adiponectin receptor-1 C-terminal Fragment (CTF) in plasma: putative biomarker for diabetes. Clin Proteom 2009;5:156-62. https://doi.org/10.1007/s12014-009-9036-1
  12. Neyzi O, Bundak R, Gokcay G, Gunoz H, Furman A, Darendeliler F, et al. Reference values for weight, height, head circumference, and body mass index in Turkish children. J Clin Res Pediatr Endocrinol 2015;7:280-93. https://doi.org/10.4274/jcrpe.2183
  13. Rumack CM, Charboneau JW, Wilson SR. Diagnostic ultrasound. 2nd ed. St. Louis, MO: Mosby, 1998:110-2.
  14. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-9. https://doi.org/10.1007/BF00280883
  15. Santas F, Santas G. Prevalence of pre-school children for overweight/obesity in Turkey. World J Pediatr 2018;14:77-83. https://doi.org/10.1007/s12519-017-0103-9
  16. Fu JF, Shi HB, Liu LR, Jiang P, Liang L, Wang CL, et al. Non-alcoholic fatty liver disease: an early mediator predicting metabolic syndrome in obese children? World J Gastroenterol 2011;17:735-42. https://doi.org/10.3748/wjg.v17.i6.735
  17. Vos MB, Abrams SH, Barlow SE, Caprio S, Daniels SR, Kohli R, et al. NASPGHAN clinical practice guideline for the diagnosis and treatment of nonalcoholic fatty liver disease in children: recommendations from the expert committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). J Pediatr Gastroenterol Nutr 2017;64:319-34. https://doi.org/10.1097/MPG.0000000000001482
  18. Fang YL, Chen H, Wang CL, Liang L. Pathogenesis of non-alcoholic fatty liver disease in children and adolescence: from “two hit theory” to “multiple hit model”. World J Gastroenterol 2018;24:2974-83. https://doi.org/10.3748/wjg.v24.i27.2974
  19. Polyzos SA, Toulis KA, Goulis DG, Zavos C, Kountouras J. Serum total adiponectin in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Metabolism 2011;60:313-26. https://doi.org/10.1016/j.metabol.2010.09.003
  20. Dermitzaki E, Avgoustinaki PD, Spyridaki EC, Simos P, Malliaraki N, Venihaki M, et al. Adiponectin levels may help assess the clinical repercussions of obesity irrespective of body mass index. Hormones (Athens) 2017;16:271-81. https://doi.org/10.1007/BF03401521
  21. Slutsky N, Vatarescu M, Haim Y, Goldstein N, Kirshtein B, Harman-Boehm I, et al. Decreased adiponectin links elevated adipose tissue autophagy with adipocyte endocrine dysfunction in obesity. Int J Obes (Lond) 2016;40:912-20. https://doi.org/10.1038/ijo.2016.5
  22. Jimenez-Rivera C, Hadjiyannakis S, Davila J, Hurteau J, Aglipay M, Barrowman N, et al. Prevalence and risk factors for non-alcoholic fatty liver in children and youth with obesity. BMC Pediatr 2017;17:113. https://doi.org/10.1186/s12887-017-0867-z
  23. Boutari C, Perakakis N, Mantzoros CS. Association of adipokines with development and progression of nonalcoholic fatty liver disease. Endocrinol Metab (Seoul) 2018;33:33-43. https://doi.org/10.3803/EnM.2018.33.1.33
  24. Moschen AR, Wieser V, Tilg H. Adiponectin: key player in the adipose tissue-liver crosstalk. Curr Med Chem 2012;19:5467-73. https://doi.org/10.2174/092986712803833254
  25. Pirvulescu I, Gheorghe L, Csiki I, Becheanu G, Dumbrava M, Fica S, et al. Noninvasive clinical model for the diagnosis of nonalcoholic steatohepatitis in overweight and morbidly obese patients undergoing bariatric surgery. Chirurgia (Bucur) 2012;107:772-9.
  26. Verhaegh P, Bavalia R, Winkens B, Masclee A, Jonkers D, Koek G. Noninvasive tests do not accurately differentiate nonalcoholic steatohepatitis from simple steatosis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2018;16:837-61. https://doi.org/10.1016/j.cgh.2017.08.024
  27. Oana F, Takeda H, Matsuzawa A, Akahane S, Isaji M, Akahane M. Adiponectin receptor 2 expression in liver and insulin resistance in db/db mice given a beta3-adrenoceptor agonist. Eur J Pharmacol 2005;518:71-6. https://doi.org/10.1016/j.ejphar.2005.06.004
  28. Matsunami T, Sato Y, Ariga S, Sato T, Kashimura H, Hasegawa Y, et al. Regulation of oxidative stress and inflammation by hepatic adiponectin receptor 2 in an animal model of nonalcoholic steatohepatitis. Int J Clin Exp Pathol 2010;3:472-81.
  29. Potapov VA, Chistiakov DA, Dubinina A, Shamkhalova MS, Shestakova MV, Nosikov VV. Adiponectin and adiponectin receptor gene variants in relation to type 2 diabetes and insulin resistance-related phenotypes. Rev Diabet Stud 2008;5:28-37. https://doi.org/10.1900/RDS.2008.5.28
  30. Musso G, Cassader M, Paschetta E, Gambino R. Thiazolidinediones and advanced liver fibrosis in nonalcoholic steatohepatitis: a meta-analysis. JAMA Intern Med 2017;177:633-40. https://doi.org/10.1001/jamainternmed.2016.9607
  31. Zhang YN, Fowler KJ, Hamilton G, Cui JY, Sy EZ, Balanay M, et al. Liver fat imaging-a clinical overview of ultrasound, CT, and MR imaging. Br J Radiol 2018;91:20170959.

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