Retinol binding protein-4 as a serum biomarker of intrahepatic lipid content in obese children - preliminary report
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Objectives: Obesity, insulin resistance and dyslipidemia are the most significant risk factors of non-alcoholic fatty liver disease (NAFLD) but the role of adipokines in the pathogenesis of this disease is not clear. Assessment of retinol binding protein (RBP-4) seems to be promising because data from animal and human studies suggest its role in the patomechanism of insulin resistance. Therefore, the aim of the study was to evaluate the serum levels of RBP-4 in children with NAFLD. Methods: Fasting serum level of RBP-4 was determined in 42 obese children with suspected liver disease and 20 lean controls. The degree of liver steatosis was graded in ultrasound according to Saverymuttu. The intrahepatic lipid content was assessed noninvasively in a semiquantitative fashion using 1HMR spectroscopy (1.5-T scanner with PRESS sequence). Results: Fatty liver was confirmed in 30 children by ultrasonography (16 of them had also increased alanine transaminase (ALT) activity). Serum concentrations of RBP-4 were significantly higher in obese children with NAFLD compared to controls. Significant correlations were found between RBP-4 level and ultrasonographic grade of liver steatosis, intrahepatic lipid content (1HMRS) and triglycerides level, while the serum level of RBP-4 was not significantly higher in children with advanced liver steatosis (grade 2-3, n = 11) compared to patients with mild steatosis (grade 1, n = 19). The ability of RBP-4 to differentiate children with advanced liver steatosis from those with mild steatosis was not significant. Conclusion: RBP-4 can be considered as a convenient serum marker of intrahepatic lipid content in obese children.
- Alkhouri N, Lopez R, Berk M, Feldstein AE (2009) Serum retinol-binding protein 4 levels in patients with nonalcoholic fatty liver disease. J Clin Gastroenterol 43: 985-989.
- Angulo P (2002) Nonalcoholic fatty liver disease. N Engl J Med 346: 1221-1231.
- Argo CK, Caldwell SH (2009) Epidemiology and natural history of non-alcoholic steatohepatitis. Clin Liver Dis 13: 511-531.
- Cengiz C, Ardicoglu Y, Bulut S, Boyacioglu S (2009) Serum retinol-binding protein 4 in patients with nonalcoholic fatty liver disease: does it have a significant impact on pathogenesis? Eur J Gastroenterol Hepatol 22: 813-819.
- Graham TE, Wason CJ, Blüher M, Kahn BB (2007) Shortcomings in methodology complicate measurements of serum retinol binding protein (RBP4) in insulin-resistant human subjects. Diabetologia 50: 814-823.
- Joy D, Thava VR, Scott BB (2003) Diagnosis of fatty liver disease: is biopsy necessary? Eur J Gastroenterol Hepatol 15: 539-543.
- Kershaw EF, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89: 2548-2556.
- Lebensztejn DM, Wojtkowska M, Skiba E, Werpachowska I, Tobolczyk J, Kaczmarski M (2009) Serum concentration of adiponectin, leptin and resistin in obese children with non-alcoholic fatty liver disease. Adv Med Sci 54: 177-182.
- Loomba R, Sirlin CB, Lavine JE (2009) Advances in pediatric nonalcoholic fatty liver disease. Hepatology 50: 1282-1293.
- Louthan MV, Barve S, McClain CJ, Joshi-Barve S (2005) Decreased serum adiponectin: an early event in pediatric nonalcoholic fatty liver disease. J Pediatr 147: 835-838.
- Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentration in man. Diabetologia 28: 412-419.
- Milner K-L, van der Poorten D, Bugianesi E, Kench JG, Lam KSL, Chisholm DJ et al (2009) Adipocyte fatty acid binding protein levels relate to inflammation and fibrosis in nonalcoholic fatty liver disease. Hepatology 49: 1926-1934.
- Nobili V, Alkhouri N, Alisi A, Ottino S, Lopez R, Manco M et al (2009) Retinol-binding protein 4: a promising circulating marker of liver damage in pediatric nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 7: 575-579.
- Patton HM, Sirling C, Behling C, Middleton M, Schwimmer JB, Lavine JE (2006) Pediatric nonalcoholic fatty liver disease: a critical appraisal of current data and implications of future research. J Pediatr Gastroenterol Nutr 43: 413-427.
- Perseghin G, Lattuada G, De Cobelli F, Esposito A, Belloni E, Canu T (2007) Serum retinol-binding protein-4, leptin, and adiponectin concentrations are related to ectopic fat accumulation. J Clin Endocrinol Metab 92: 4883-4888.
- Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E (2005) Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 128: 1898-1906.
- Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M (2002) The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 123: 745-750.
- Saverymuttu SH, Joseph AE, Maxwell JD (1986) Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J (Clin Res Ed) 292: 13-15.
- Schina M, Koskinas J, Tiniakos D, Hadziyannis E, Savvas S, Karamanos B, Manesis E, Archimandritis A (2009) Circulating and liver tissue levels of retinol-binding protein-4 in non-alcoholic fatty liver disease. Hepatol Res 39: 972-978.
- Seo JA, Kim NH, Park SY, Kim HY, Ryu OH, Lee KW et al. (2008) Serum retinol-binding protein 4 levels are elevated in non-alcoholic fatty liver disease. Clin Endocrinol (Oxf) 68: 555-560.
- Stefan N, Hennige AM, Staiger H, Machann J, Schick F, Schleicher E et al (2007) High circulating retinol-binding protein 4 is associated with elevated liver fat but not with total, subcutaneous, visceral, or intramyocellular fat in humans. Diabetes Care 30: 1173-1178.
- Tarasów E, Siergiejczyk L, Panasiuk A, Kubas B, Dzienis W, Prokopowicz D, Walecki J (2002) MR proton spectroscopy in liver examinations of healthy individuals in vivo. Med Sci Monit 8: MT36-MT40.
- Vida S (1993) A computer program for non-parametric receiver operating characteristics analysis. Comput Methods Programs Biomed 40: 95-101.
- Wu H, Jia W, Bao Y, Lu J, Zhu J, Wang R et al. (2008) Serum retinol binding protein 4 and nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 79: 185-190.
- Yagmur E, Weiskirchen R, Gressner AM, Trautwein C, Tacke F (2007) Insulin resistance in liver cirrhosis is not associated with circulating retinol-binding protein 4. Diabetes Care 30: 1168-1172.
- Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM et al. (2005) Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 436: 356-362.
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