Abstract
Aim: Nonalcoholic fatty liver disease (NAFLD) is the accumulation of excess fat in the liver in the absence of alcohol consumption, which is commonly associated with obesity and increased risk of atherosclerosis as well as insulin resistance. Adropin is a recently identified protein encoded by the gene related with energy homeostasis, which is expressed in the liver and the brain and has a role in preventing insulin resistance and obesity. The aim of this study was to investigate the serum adropin and leptin levels in obese adolescents and compare the patients with, and without, NAFLD and with healthy controls.
Methods: Sixty-four obese adolescents (30 with NAFLD, 34 without NAFLD) and 36 healthy controls were enrolled in the study. Serum adropin and leptin levels were evaluated by sandwich enzyme-linked immunosorbent assay.
Results: Serum adropin levels were significantly lower in obese children than healthy controls (3.2±1.0 and 9.2±1.2 ng/mL, respectively, p=0.001). Serum leptin levels were significantly higher in patients than in controls (12.4±1.1 and 4.1±3.1 pg/mL, respectively; p=0.000). Serum adropin levels of patients with NAFLD were significantly lower than in patients without NAFLD (2.9±0.5 and 3.5±1.2 ng/mL, respectively; p=0.023) and healthy controls (p=0.000). Logistic regression analysis showed that a decrease in adropin levels was the only independent factor for fatty liver disease in obese adolescents (odds ratio: 3.07, 95% confidence interval 1.14–8.2, p=0.026). Leptin, relative weight and HOMA-IR of the patients were not independent risk factors for NAFLD.
Conclusions: In this study, serum adropin levels were significantly lower in obese adolescents with fatty liver disease compared to patients without fatty liver disease and healthy controls. Lower adropin level was an independent risk factor for NAFLD in obese adolescents in logistic regression analysis. Assessment of serum adropin concentrations may provide a reliable indicator of fatty liver disease in obese adolescents.
Acknowledgments
This study was supported by a grant (KB.SAG.047) from Dokuz Eylul University Funding Committee for Scientific Research, Izmir, Turkey. We acknowledge the support of the ARLAB (Research Laboratory) of Dokuz Eylül University Medical School, Izmir, Turkey.
Conflict of interest statement: The authors have no relevant conflict of interest to disclose.
References
1. Arslan N, Tokgoz Y, Kume T, Bulbul M, Sayın O, et al. Evaluation of serum neopterin levels and its relationship with adipokines in pediatric obesity-related nonalcoholic fatty liver disease and healthy adolescents. J Pediatr Endocrinol Metab 2013;26:1141–7.10.1515/jpem-2013-0029Search in Google Scholar
2. Arslan N, Makay B. Mean platelet volume in obese adolescents with nonalcoholic fatty liver disease. J Pediatr Endocrinol Metab 2010;23:807–13.10.1515/jpem.2010.130Search in Google Scholar
3. Mencin AA, Lavine JE. Nonalcoholic fatty liver disease in children. Curr Opin Clin Nutr Metab Care 2011;14:151–7.Search in Google Scholar
4. Aly FZ, Kleiner DE. Update on fatty liver disease and steatohepatitis. Adv Anat Pathol 2011;18:294–300.10.1097/PAP.0b013e318220f59bSearch in Google Scholar
5. Arslan N, Erdur B, Aydın A. Hormones and cytokines in childhood obesity. Indian Pediatr 2010;47:829–39.10.1007/s13312-010-0142-ySearch in Google Scholar
6. Siegrist M, Rank M, Wolfarth B, Langhof H, Haller B, et al. Leptin, adiponectin, and short-term and long-term weight loss after a lifestyle intervention in obese children. Nutrition 2013;29:851–7.10.1016/j.nut.2012.12.011Search in Google Scholar
7. Wang Q, Yin J, Xu L, Cheng H, Zhao X, et al. Prevalence of metabolic syndrome in a cohort of Chinese schoolchildren: comparison of two definitions and assessment of adipokines as components by factor analysis. BMC Public Health 2013;13:249.10.1186/1471-2458-13-249Search in Google Scholar
8. Kumar KG, Trevaskis JL, Lam DD, Sutton GM, Koza RA, et al. Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab 2008;8:468–81.10.1016/j.cmet.2008.10.011Search in Google Scholar
9. Lian W, Gu X, Qin Y, Zheng X. Elevated plasma levels of adropin in heart failure patients. Intern Med 2011;50:1523–7.10.2169/internalmedicine.50.5163Search in Google Scholar
10. Aydin S, Kuloglu T, Aydin S, Eren MN, Yilmaz M, et al. Expression of adropin in rat brain, cerebellum, kidneys, heart, liver, and pancreas in streptozotocin-induced diabetes. Mol Cell Biochem 2013;380:73–81.10.1007/s11010-013-1660-4Search in Google Scholar
11. Aydin S. Presence of adropin, nesfatin-1, apelin-12, ghrelins and salusins peptides in the milk, cheese whey and plasma of dairy cows. Peptides 2013;43:83–7.10.1016/j.peptides.2013.02.014Search in Google Scholar
12. Gozal D, Kheirandish-Gozal L, Bhattacharjee R, Molero-Ramirez H, Tan HL, et al. Circulating adropin concentrations in pediatric obstructive sleep apnea: potential relevance to endothelial function. J Pediatr 2013;163:1122–6.10.1016/j.jpeds.2013.05.040Search in Google Scholar
13. Celik A, Balin M, Kobat MA, Erdem K, Baydas A, et al. Deficiency of a new protein associated with cardiac syndrome X; called adropin. Cardiovasc Ther 2013;31:174–8.10.1111/1755-5922.12025Search in Google Scholar
14. Celik E, Yilmaz E, Celik O, Ulas M, Turkcuoglu I, et al. Maternal and fetal adropin levels in gestational diabetes mellitus. J Perinat Med 2013;41:375–80.10.1515/jpm-2012-0227Search in Google Scholar
15. Butler AA, Tam CS, Stanhope KL, Wolfe BM, Ali MR, et al. Low circulating adropin concentrations with obesity and aging correlate with risk factors for metabolic disease and increase after gastric bypass surgery in humans. J Clin Endocrinol Metab 2012;97:3783–91.10.1210/jc.2012-2194Search in Google Scholar
16. Strauss RS. Childhood obesity. Pediatr Clin North Am 2002;49:175–201.10.1016/S0031-3955(03)00114-7Search in Google Scholar
17. Shannon A, Alkhouri N, Carter-Kent C, Monti L, Devito R, et al. Ultrasonographic quantitative estimation of hepatic steatosis in children with NAFLD. J Pediatr Gastroenterol Nutr 2011;53:190–5.10.1097/MPG.0b013e31821b4b61Search in Google Scholar
18. Quinn SF, Gosink BB. Characteristic sonographic signs of hepatic fatty infiltration. AJR Am J Roentgenol 1985;145:753–5.10.2214/ajr.145.4.753Search in Google Scholar
19. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–9.10.1007/BF00280883Search in Google Scholar
20. Kumar KG, Zhang J, Gao S, Rossi J, McGuinness OP, et al. Adropin deficiency is associated with increased adiposity and insulin resistance. Obesity (Silver Spring) 2012;20:1394–402.10.1038/oby.2012.31Search in Google Scholar
21. Ruiz-Extremera Á, Carazo Á, Salmerón Á, León J, Casado J, et al. Factors associated with hepatic steatosis in obese children and adolescents. J Pediatr Gastroenterol Nutr 2011;53:196–201.10.1097/MPG.0b013e3182185ac4Search in Google Scholar
22. Kim IK, Kim J, Kang JH, Song J. Serum leptin as a predictor of fatty liver in 7-year-old Korean children. Ann Nutr Metab 2008;53:109–16.10.1159/000165360Search in Google Scholar
23. Canas JA, Damaso L, Altomare A, Killen K, Hossain J, et al. Insulin resistance and adiposity in relation to serum β-carotene levels. J Pediatr 2012;161:58–64.10.1016/j.jpeds.2012.01.030Search in Google Scholar
24. Gherlan I, Vladoiu S, Alexiu F, Giurcaneanu M, Oros S, et al. Adipocytokine profile and insulin resistance in childhood obesity. Maedica (Buchar) 2012;7:205–13.Search in Google Scholar
25. Pacifico L, Bezzi M, Lombardo CV, Romaggioli S, Ferraro F, et al. Adipokines and C-reactive protein in relation to bone mineralization in pediatric nonalcoholic fatty liver disease. World J Gastroenterol 2013;19:4007–14.10.3748/wjg.v19.i25.4007Search in Google Scholar
26. Fitzpatrick E, Dew TK, Quaglia A, Sherwood RA, Mitry RR, et al. Analysis of adipokine concentrations in paediatric non-alcoholic fatty liver disease. Pediatr Obes 2012;7:471–9.10.1111/j.2047-6310.2012.00082.xSearch in Google Scholar
27. Lebensztejn DM, Wojtkowska M, Skiba E, Werpachowska I, Tobolczyk J, et al. Serum concentration of adiponectin, leptin and resistin in obese children with non-alcoholic fatty liver disease. Adv Med Sci 2009;54:177–82.10.2478/v10039-009-0047-ySearch in Google Scholar
28. Machado MV, Coutinho J, Carepa F, Costa A, Proença H, et al. How adiponectin, leptin, and ghrelin orchestrate together and correlate with the severity of nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2012;24:1166–72.10.1097/MEG.0b013e32835609b0Search in Google Scholar
29. Mager DR, Yap J, Rodriguez-Dimitrescu C, Mazurak V, Ball G, et al. Anthropometric measures of visceral and subcutaneous fat are important in the determination of metabolic dysregulation in boys and girls at risk for nonalcoholic fatty liver disease. Nutr Clin Pract 2013;28:101–11.10.1177/0884533612454884Search in Google Scholar
30. Fitzpatrick E, Mitry RR, Quaglia A, Hussain MJ, DeBruyne R, et al. Serum levels of CK18 M30 and leptin are useful predictors of steatohepatitis and fibrosis in paediatric NAFLD. J Pediatr Gastroenterol Nutr 2010;51:500–6.10.1097/MPG.0b013e3181e376beSearch in Google Scholar
31. Arslan N, Büyükgebiz B, Oztürk Y, Cakmakçi H. Fatty liver in obese children: prevalence and correlation with anthropometric measurements and hyperlipidemia. Turk J Pediatr 2005;47:23–7.Search in Google Scholar
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