2016, Number 6
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Ann Hepatol 2016; 15 (6)
Chemerin, retinol binding protein-4, cytokeratin-18 and transgelin-2 presence in sera of patients with non-alcoholic liver fatty disease
Zwolak A, Szuster-Ciesielska A, Daniluk J, Semeniuk J, Kandefer-Szerszen M
Language: English
References: 41
Page: 862-869
PDF size: 239.17 Kb.
ABSTRACT
Background. Chemerin and retinol binding protein-4 (RBP-4) are adipokines which may play a role in the progression of NAFLD. It
has been also suggested that cytokeratin-18 (CK-18) could be a marker of hepatocyte caspase-directed death while transgelin-2 production
could reflect stage of liver fibrosis. The aim of this study was to evaluate the level of the above adipokines in sera of patients
with NAFLD and determine the relation between the level of transgelin-2 and fibrosis-4 index (FIB-4).
Material and methods.
Ninety-five subjects included initially to the study were divided into four groups: (I) prediabetics, obese with NAFLD and metabolic
syndrome (MS), (II) lean with NAFLD and without MS, (III) obese without NAFLD and MS, and (IV) healthy individuals. We determined
the levels of chemerin, RBP-4, transgelin-2 and CK-18 fragments in sera of patients with NAFLD. Moreover, we examined if
the levels of CK-18 fragments and transgelin-2 correlates with FIB4 value.
Results. Chemerin and RBP-4 were highly expressed in
sera of all NAFLD, especially in obese individuals. Chemerin level was also linked to MS. High level of serum CK-18 fragments and
transgelin-2 did not correlate with obesity and MS, but seemed to correlate with progression of NAFLD to liver fibrosis.
Conclusions.
In conclusion, the production of the two adipokines, chemerin and RBP-4, is strongly associated with obesity in patients with
NAFLD. Serum concentrations of CK-18 fragments and transgelin-2 correlate with the severity of NAFLD, but not with obesity.
REFERENCES
Hassan K, Bhalla V, El Regal ME, A-Kader HH. Nonalcoholic fatty liver disease: a comprehensive review of a growing epidemic. World J Gastroenterol 2014; 20: 12082-101.
Abenavoli L, Peta V. Role of adipokines and cytokines in non-alcoholic fatty liver disease. Rev Recent Clin Trials 2014; 9: 134-40.
Tsochatzis EA, Papatheodoridis GV, Archimandritis AJ. Adipokines in nonalcoholic steatohepatitis: from pathogenesis to implications in diagnosis and therapy. Mediators Inflamm 2009, 2009: 831670. Doi: 10.1155/2009/831670.
Lemoine M, Ratziu V, Kim M, Maachi M, Wendum D, Paye F, Bastard JP, et al. Serum adipokine levels predictive of liver injury in non-alcoholic fatty liver disease. Liver Int 2009; 29: 1431-8.
Krawczyk K, Szczesniak P, Kumor A, Jasinska A, Omulecka A, Pietruczuk M, Orszulak-Michalak D, et al. Adipohormones as prognostic markers in patients with nonalcoholic steatohepatitis (NASH). J Physiol Pharmacol 2009; 60: 71-5.
Marra F, Bertolani C. Adipokines in liver diseases. Hepatology 2009; 50: 957-69.
Terra X, Auguet T, Broch M, Sabench F, Hernández M, Pastor RM, Quesada IM, et al. Retinol binding protein-4 circulating levels were higher in nonalcoholic fatty liver disease vs. histologically normal liver from morbidly obese women. Obesity 2013; 21: 170-7.
Romanowska A, Lebensztejn DM, Skiba E, Tarasow E, Kaczmarski M. Retinol binding protein-4 as a serum biomarker of intrahepatic lipid content in obese children—preliminary report. Acta Biochim Pol 2011; 58: 35-8.
Broch M, Gómez JM, Auguet MT, Vilarrasa N, Pastor R, Elio I, Olona M, et al. Association of retinol-binding protein-4 (RBP4) with lipid parameters in obese women. Obes Surg 2010; 20: 1258-64.
Maher JJ. Retinol binding protein 4 and fatty liver: A direct link? Hepatology 2013; 58: 477-9.
Alkhouri N, Lopez R, Berk M, Feldstein AE. Serum retinolbinding protein 4 levels in patients with nonalcoholic fatty liver disease. J Clin Gastroenterol 209; 43: 985-9.
Kotnik P, Fischer-Posovszky P, Wabitsch M. RBP4: a controversial adipokine. Eur J Endocrinol 2011; 165: 703-11.
Marra F, Bertolani C. Adipokines in liver diseases. Hepatology 2009; 50: 957-69.
Döcke S, Lock JF, Birkenfeld AL, Hoppe S, Lieske S, Rieger A, Raschzok N, et al. Elevated hepatic chemerin mRNA expression in human non-alcoholic fatty liver disease. Eur J Endocrinol 2013; 169: 547-57.
Deng Y, Wang H, Lu Y, Liu S, Zhang Q, Huang J, Zhu R, et al. Identification of chemerin as a novel FXR target gene down-regulated in the progression of nonalcoholic steatohepatitis. Endocrinology 2013; 154: 1794-801.
Stejskal D, Karpisek M, Hanulova Z, Svestak M. Chemerin is an independent marker of the metabolic syndrome in a Caucasian population—a pilot study. Biomedl Pap Med Fac Univ Palacky Olomouc, Czech Repub 2008; 152: 217-21.
Li Y, Shi B, Li S. Association between serum chemerin concentrations and clinical indices in obesity or metabolic syndrome: a meta-analysis. PLoS One 2014; 9: 12, e113915. Doi: 10.1371.
Apte MV, Yang L, Phillips PA, Xu Z, Kaplan W, Cowley M, Pirola RC, et al. Extracellular matrix composition significantly influences pancreatic stellate cell gene expression pattern: role of transgelin in PSC function. Am J Physiol Gastrointest Liver Physiol 2013; 305: G408-G417.
Feldstein AE, Wieckowska A, Lopez AR, Liu YC, Zein NN, McCullough AJ. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology 2009; 50: 1072-8.
Dyson J K, McPherson S, Anstee QM. Non-alcoholic fatty liver disease: non-invasive investigation and risk stratification. J Clin Pathol 2013; 66: 1033-45.
Imbert-Bismut F, Ratziu V, Pieroni L, MULTIVIRC Group. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet 2001; 357: 1069-75.
Rossi E, Adams L, Prins A, Bulsara M, de Boer B, Garas G, MacQuillan G, et al. Validation of the FibroTest biochemical markers score in assessing liver fibrosis in hepatitis C patients. Clinl Chem 2003; 49: 450-4.
Mansoor S, Collyer E, Alkhouri N. A comprehensive review of noninvasive liver fibrosis tests in pediatric nonalcoholic Fatty liver disease. Curr Gastroenterol Rep 2015; 17: 447, 2015. Doi: 10.1007/s11894-015-0447-z.
Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, Sulkowski M, et al. Development of a simple noninvasive index to predict significant fibrosis patients with HIV/HCV co-infection. Hepatology 2006; 43: 1317-25.
Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, et al. Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41: 1313-21.
Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999; 116(6): 1413-9.
Bullard KM, Saydah SH, Imperatore G, Cowie CC, Gregg EW, Geiss LS, Cheng YJ, et al. Secular changes in U.S. Prediabetes prevalence defined by hemoglobin A1c and fasting plasma glucose: National Health and Nutrition Examination Surveys. Diab Care 2013; 36: 2286-93.
Bednarek-Tupikowska G, Stachowska B, Miazgowski T, Krzyzanowska-Swiniarska B, Katra B, Jaworski M, Kuliczkowska- Plaksej J, et al. Evaluation of the prevalence of metabolic obesity and normal weight among the Polish population. Endokrynol Pol 2012; 63(6): 447-55.
Lee JH, Kim D, Kim HJ, Lee CH, Yang JI, Kim W, Kim YJ, et al. Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease. Dig Liver Dis 2010; 42: 503-8.
Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, Tiribelli C. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterology 2006; 2: 33.
Zwolak A, Slabczynska O, Semeniuk J, Daniluk J, Szuster- Ciesielska A. Metformin changes relationship between blood monocyte Toll-like receptor 4 levels and nonalcoholic fatty liver disease – ex vivo studies. Mediators of Inflammation (study send to press).
Bozaoglu K, Curran JE, Elliott KS, Walder KR, Dyer TD, Rainwater DL, VandeBerg JL, et al. Association of genetic variation within UBL5 with phenotypes of metabolic syndrome. Hum Biol 2006; 78: 147-59.
Zhuang X, Sun F, Li L, Jiang D, Li X, Sun A, Pan Z, et al. Therapeutic Effect of Metformin on Chemerin in Non-Obese Patients with Non-Alcoholic Fatty Liver Disease (NAFLD). Clin Lab 2015; 61:1409-14.
Döcke S, Lock JF, Birkenfeld AL, Hoppe S, Lieske S, Rieger A, Raschzok N, et.al. Elevated hepatic chemerin mRNA expression in human non-alcoholic fatty liver disease. Eur J Endocrinol 2013; 169: 547-57.
Polyzos SA, Kountouras J, Mantzoros CS. Adipokines in nonalcoholic fatty liver disease. Metabolism 2015; 24. pii: S0026-0495(15)00351-0. Doi: 10.1016/j.metabol.2015.11.006 [Epub ahead of print].
Wolf G. Serum retinol-binding protein: a link between obesity, insulin resistance, and type 2 diabetes. Nutr Rev 2007; 65: 251-6.
Janke J, Engeli S, Boschmann M, Adams F, Böhnke J, Luft FC, Sharma AM, et al. Retinol-binding protein 4 in human obesity. Diabetes 2006; 55: 2805-10.
Cusi K, Chang Z, Harrison S, Lomonaco R, Bril F, Orsak B, Ortiz-Lopez C, et al. Limited value of plasma cytokeratin-18 as a biomarker for NASH and fibrosis in patients with nonalcoholic fatty liver disease. J Hepatol 2014; 60: 167-74.
Miyasato M, Murase-Mishiba Y, Bessho M, Miyawaki M, Imbe H, Tsutsumi C, Tanimoto K, et al. The cytokeratin-18 fragment level as a biomarker of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. Clin Chim Acta 2014; 433: 184-9.
Mölleken C, Sitek B, Henkel C, Poschmann G, Sipos B, Wiese S, Warscheid B, et al. Detection of novel biomarkers of liver cirrhosis by proteomic analysis. Hepatology 2009; 49: 1257-66.
Nuńo-Lámbarri N, Barbero-Becerra VJ, Uribe M, Chávez- Tapia NC. Mitochondrial Molecular Pathophysiology of Nonalcoholic Fatty Liver Disease: A Proteomics Approach. Int J Mol Sci 2016; 17: pii: E281. Doi: 10.3390/ijms17030281.