Chemerin as a novel non-invasive serum marker of intrahepatic lipid content in obese children

Italian Journal of Pediatrics

Dariusz Marek Lebensztejn³  Irena Werpachowska³  Malgorzata Wojtkowska¹  Eugeniusz Tarasów⁴  Irena Bialokoz-Kalinowska²  Monika K?usek-Oksiuta³ 

[1] Department of Radiology, University Teaching Children¿s Hospital, Bialystok, Poland;Department of Pediatrics and Developmental Disorders, Medical University of Bialystok, Bialystok, Poland;Department of Pediatrics, Gastroenterology and Allergology, Medical University of Bialystok, 17 Waszyngtona St., Bialystok 15-274, Poland;Department of Radiology, Medical University of Bialystok, Bialystok, Poland

关键词: Children;    NAFLD;    Intrahepatic lipid content;    Vaspin;    Omentin;    Chemerin;    Adipokines;   

Others  :  1146234
DOI  :  10.1186/s13052-014-0084-4

 received in 2014-06-03, accepted in 2014-10-12,  发布年份 2014

【 摘 要 】

Background

Ectopic hepatic lipid accumulation is closely related to the development of insulin resistance, which is regarded as one of the most significant risk factors of non-alcoholic fatty liver disease (NAFLD). The current study has shown that fat tissue constitutes an important endocrine organ with its own production and metabolism of many biologically active substances, among which adipokines play an important role. Classic adipokines (e.g. leptin, adiponectin, resistin) are fat-derived hormones which serum level is altered in patients with NAFLD. The role of novel adipokines in the pathomechanism of this disease is not clear. Therefore, the aim of our study was to evaluate the serum concentrations of chemerin, omentin and vaspin in obese children with NAFLD.

Methods

Forty-five obese children, aged 7¿17 years old, were admitted to our Department with suspected liver disease (hepatomegaly, and/or ultrasonographic liver brightness, and/or increased ALT activity). Viral hepatitides, as well as autoimmune and metabolic liver diseases were excluded. Fasting serum levels of chemerin, omentin and vaspin were determined. The grade of liver steatosis in ultrasound was graded according to Saverymuttu. ¹HMR spectroscopy was performed with a 1.5 T scanner and with PRESS sequencing.

Results

Fatty liver was confirmed in 39 children by ultrasound and in 33 patients by ¹HMRS (19 of them also had increased ALT activity /NAFLD/). Chemerin and vaspin levels were significantly higher in children with NAFLD compared to the control group (n?=?30). The concentration of chemerin was significantly higher in children with advanced liver steatosis compared to non-hepatopathic patients (p?=?0,02). Significant positive correlations were found between the total liver lipids in ¹HMRS and chemerin (r?=?0,33; p?=?0,02) and vaspin (r?=?0,4; p?=?0,006). The ability of serum chemerin (cut-off?=?190 ng/ml, Se?=?75%, Sp?=?58%) to differentiate children with fatty liver in ¹HMRS from those without steatosis was significant (AUC?=?0,7, p?=?0,04). Omentin and vaspin did not allow a useful prediction to be made.

Conclusion

Chemerin seems to be the most suitable non-invasive biomarker in predicting both intrahepatic lipid content in obese children and advanced liver steatosis in children with NAFLD.

【 授权许可】

   
2014 Klusek-Oksiuta et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Giorgio V, Pruno E, Graziano F, Nobili V: Pediatric non alcoholic fatty liver disease: old and new concept on development, progression, metabolic insight and potential treatment target. BMC Pediatr 2013, 13:40. BioMed Central Full Text
• [2]Pacifico L, Nobili V, Anania C, Verdecchia P, Chiesa C: Pediatric nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular risk. World J Gastroenterol 2011, 17:3082-3091.
• [3]Targher G, Day CP, Bonora E: Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Eng J Med 2011, 363:1341-1350.
• [4]Alkhouri N, Carter-Kent C, Elias M, Feldstein AE: Atherogenic dyslipidemia and cardiovascular risk in children with nonalcoholic fatty liver disease. Clin Lipidiol 2011, 6:305-314.
• [5]Fox CS, Massaro JM, Hoffmann U, Pou K, Maurovich-Horvath O, Liu CY, Vasan RS, Murabito JM, Meigs JB, Cupples LA, D¿Agostino RB, O¿Donnell CJ: Abdominal, visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 2007, 116:39-48.
• [6]Speliotes F, Massaro JM, Hoffmann U, Vasan RS, Meigs JB, Sahani DV, Hirschhorn JN, O¿Donnell CJ, Fox CS: Fatty liver is associated with dyslipidemia and dysglycemia independent of visceral fat: the Framingham Heart Study. Hepatology 2010, 51:1979-1987.
• [7]Lim S, Meighs JB: Ectopic fat and cardiometabolic and vascular risk. Int J Cardiol 2013, 169:166-176.
• [8]Kershaw EE, Flier JS: Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004, 89:2548-2556.
• [9]Kukla M, Zwirska-Korczala K, Hartleb M, Waluga M, Chwist A, Kajor M, Ciupinska-Kajor M, Berdowska A, Wozniak-Grygiel E, Buldak R: Serum chemerin and vaspin in non-alcoholic fatty liver disease. Scand J Gastroenterol 2010, 45:235-242.
• [10]Yilmaz Y, Yonal O, Kurt R, Alahdab YO, Eren F, Ozdagan O, Celikel CA, Imeryuz N, Kalayci C, Avsar E: Serum levels of omentin, chemerin and adipsin in patients with biopsy-proven nonalcoholic fatty liver disease. Scan J Gastroenterol 2011, 46:91-97.
• [11]Aktas B, Yilmaz Y, Eren F, Yonal O, Kurt R, Alahdab YO, Celikel CA, Ozdogan O, Imeryuz N, Kalayci C, Avsar E: Serum levels of vaspin, obestatin, and apelin-36 in patients with nonalcoholic fatty liver disease. Metabol Clin Experimental 2011, 60:544-549.
• [12]Yilmaz Y, Kurt R, Gurdal A, Alahdab YO, Yonal D, Senates E, Polat N, Eren F, Imeryuz N, Oflan H: Circulating vaspin levels and epicardial adipose tissue thickness are associated with impaired coronary flow reserve in patients with nonalcoholic fatty liver disease. Atherosclerosis 2011, 217:125-129.
• [13]Lebensztejn DM, Bia?okoz-Kalinowska I, K?usek-Oksiuta M, Tarasow E, Wojtkowska M, Kaczmarski M: Serum fetuin A concentration is elevated in children with non-alcoholic fatty liver disease. Adv Med Sci 2014, 59:81-84.
• [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 concentration in man. Diabetologia 1985, 28:412-419.
• [15]Saverymuttu SH, Joseph AE, Maxwell JD: Ultrasound Canning in the detection of hepatic fibrosis and steatosis. Br Med J 1986, 292:13-15.
• [16]Tarasów E, Siergiejczyk L, Panasiuk A, Kubas B, Dzienis W, Prokopowicz D, Walecki J: MR proton spectroscopy in liver examination of healthy individuals in vivo. Med Sci Monit 2002, 8:36-40.
• [17]Hanley JA, Hajian-Tilaki KO: Sampling variability of nonparametric estimates of the areas under receiver operating characteristic curves: an update. Acad Radiol 1997, 4:49-58.
• [18]Sell H, Divoux A, Poitou C, Basdevanta A, Bouillot JL, Bedossa P, Tordjman J, Eckel J, Clement K: Chemerin correlates with markers for fatty liver in morbidly obese patients and strongly decreases after weight loss induced by bariatric surgery. J Clin Endocrinol Metab 2010, 95:2892:6.
• [19]Yilmaz Y, Yonal O, Kurt R, Alahdab YO, Eren F, Ozdogan O, Celikel CA, Imeryuz N, Kalayci C, Avsar E: Serum levels of omentin and adipsin in patients with biopsy-proven nonalcoholic fatty liver disease. Scand J Gastroenterol 2011, 46:91-97.
• [20]Genc H, Dogru T, Tapan S, Kara M, Ercin CN, Aslan F, Kantarcioglu M, Karslioglu Y, Sertoglu E, Erbil MK, Bagci S: Circulating vaspin and its relationship with insulin sensitivity, adiponectin, and liver histology in subjects with non-alcoholic steatohepatitis. Scand J Gastroenterol 2011, 46:1355-1361.
• [21]Ye Z, Wang S, Yang Z, He M, Zhang S, Zhang W, Wen J, Li Q, Huang Y, Wang X, Lu B, Zhang Z, Su Q, Hu R: Serum lipocalin-2, cathepsin S and chemerin levels and nonalcoholic fatty liver disease. Mol Biol Rep 2014, 41:1317-1323.
• [22]Chen H-Y, Lin C-C, Chiu Y-L, Hsu SP, Pai MF, Yang JY, Peng YS: Serum fetuin A and chemerin levels correlate with hepatic steatosis and regional adiposity in maintenance hemodialysis patients. PlosONE 2012, 7:e38415.
• [23]Pozzato C, Radelli G, Dall¿Asta C, Veduci E, Villa A, Villa C, Scaglioni S, Riva E, Pontiroli AE, Cornalba G, Giovannini M: MRI in identifying hepatic steatosis in obese children and relations to ultrasonography and metabolic findings. J Pediatr Gastroenterol Nutr 2008, 47:493-499.
• [24]Schwenzer NF, Springer F, Schraml C, Stefan N, Machann J, Schick F: Non-invasive assessment and quantification of liver steatosis by ultrasound, computed tomography, and magnetic resonance. J Hepatol 2009, 51:433-445.
• [25]Vajro P, Lenta S, Socha P, Dhawan A, McKiernan P, Baumann U, Durmaz O, Lacaille F, McLin V, Nobili V: Diagnosis of nonalcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN Hepatology Committee. J Pediatr Gastroenterol Nutr 2012, 54:700-713.
• [26]Roberts EA: Pediatric nonalcoholic fatty liver disease (NAFLD): a ¿growing¿ problem? J Hepatol 2007, 46:1133-1142.
• [27]Deng Y, Wang H, Lu Y, Zhang Q, Huang J, Zhu R, Yang J, Zhang R, Zhang D, Shen W, Wing G, Yang Y: Identification of chemerin as a novel FXR target gene down-regulated in the progression of nonalcoholic steatohepatitis. Endocrinology 2013, 154:1794-1801.
• [28]Krautbauer S, Wanninger J, Eisinger K, Hader Y, Beck M, Kopp A, Schmid A, Weiss TS, Dorn C, Buechler C: Chemerin is highly expressed in hepatocytes and is induced in non-alcoholic steatohepatitis liver. Exp Mol Pathol 2013, 95:199-205.
• [29]Docke S, Lock JF, Birkenfeld AL, Koppe S, Lieske S, Rieger A, Raschzok N, Sauer IM, Florian S, Osterhoff MA, Heller R, Herrmann K, Lindenmuller S, Horn P, Bauer M, Weickert MO, Neuhaus P, Stockmann M, Mohlig M, Pfeiffer AF, von Loeffelholz C: Elevated hepatic chemerin mRNA expression in human non-alcoholic fatty liver disease. Eur J Endocrinol 2013, 169:547-557.
• [30]Schipper HS, Nuboer R, Prop S, van den HAM HJ, de Boer FK, Kesmir C, Mombers IM, van Bekkum KA, Woudstra J, Kiefl JH, Hoefer IE, de Jager W, Prakken B, van Summeren M, Kalkhoven E: Systemic inflammation in childhood obesity: circulating inflammatory mediators and activated CD 14++ monocytes. Diabetologia 2012, 55:2800-2810.
• [31]Landgraf K, Friebe D, Ulrich T, Kratzsch J, Dittrich K, Herberth G, Adams V, Kiess W, Erbs S, Korner A: Chemerin as a mediator between obesity and vascular inflammation in children. J Clin Endocrinol Metab 2012, 97:556-564.