Exp Clin Endocrinol Diabetes 2019; 127(09): 598-602
DOI: 10.1055/a-0811-9136
Article
© Georg Thieme Verlag KG Stuttgart · New York

Selenoprotein P in Patients with Nonalcoholic Fatty Liver Disease

Stergios A. Polyzos
1   First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
,
Jannis Kountouras
2   Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece
,
Maria Mavrouli
3   Department of Microbiology, National Kapodestrian University, Athens, Greece
,
Panagiotis Katsinelos
2   Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece
,
Michael Doulberis
4   Department of Internal Medicine, University Hospital Inselspital, Bern, Switzerland
,
Elpida Gavana
1   First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
,
Leonidas Duntas
5   Endocrine Unit, Evgenidion Hospital, National Kapodestrian University, Athens, Greece
› Author Affiliations
Further Information

Publication History

received 17 October 2018
revised 11 November 2018

accepted 03 December 2018

Publication Date:
09 January 2019 (online)

Abstract

Objective Main aim of this study was to evaluate circulating selenoprotein P (SEPP) levels in patients with simple steatosis (SS) and nonalcoholic steatohepatitis (NASH) compared with healthy controls.

Methods Thirty-one patients with biopsy-proven NAFLD (15 with SS, 10 with borderline NASH, 6 with definite NASH) and 27 matched controls without NAFLD were enrolled. Serum SEPP levels and liver function tests plus biochemical parameters were measured with ELISA and standard methods, respectively. Homeostatic model of assessment - insulin resistance (HOMA-IR) was calculated.

Results SEPP levels were statistically different between groups (p-value for trend=0.043). In pairwise comparisons, SEPP was lower in definite NASH compared with controls (p=0.029), but not SS (p=0.18) or borderline NASH (p=0.35). SEPP was not different between controls, SS and borderline NASH. The unadjusted trend between the controls, SS and NASH patients remained essentially unchanged after adjustment for age, sex, log(ALT) and waist circumference, but it marginally lost significance when log(HOMA-IR) entered into the model. SEPP levels were not different between groups of different severity of steatosis, fibrosis, hepatocellular ballooning, lobular and portal inflammation.

Conclusions Lower SEPP levels were observed in patients with definite NASH compared with controls, a finding warranting larger studies.

 
  • References

  • 1 Wanless IR, Lentz JS. Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology 1990; 12: 1106-1110
  • 2 Bedogni G, Miglioli L, Masutti F. et al. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology 2005; 42: 44-52
  • 3 Polyzos SA, Mantzoros CS. Nonalcoholic fatty future disease. Metabolism 2016; 65: 1007-1016
  • 4 McPherson S, Hardy T, Henderson E. et al. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management. J Hepatol 2015; 62: 1148-1155
  • 5 Piscaglia F, Svegliati-Baroni G, Barchetti A. et al. Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study. Hepatology 2016; 63: 827-838
  • 6 Park CC, Nguyen P, Hernandez C. et al. Magnetic resonance elastography vs transient elastography in detection of fibrosis and noninvasive measurement of steatosis in patients with biopsy-proven nonalcoholic fatty liver disease. Gastroenterology 2017; 152: 598-607
  • 7 Polyzos SA, Mantzoros CS. Necessity for timely noninvasive diagnosis of nonalcoholic fatty liver disease. Metabolism 2014; 63: 161-167
  • 8 Polyzos SA, Slavakis A, Koumerkeridis G. et al. Noninvasive liver fibrosis tests in patients with nonalcoholic fatty liver disease: An external validation cohort. Horm Metab Res 2018; DOI: 10.1055/a-0713-1330.
  • 9 Mintziori G, Polyzos SA. Emerging and future therapies for nonalcoholic steatohepatitis in adults. Expert Opin Pharmacother 2016; 17: 1937-1946
  • 10 Valea A, Georgescu CE. Selenoproteins in human body: focus on thyroid pathophysiology. Hormones (Athens) 2018; DOI: 10.1007/s42000-018-0033-5.
  • 11 Burk RF, Hill KE. Selenoprotein P: an extracellular protein with unique physical characteristics and a role in selenium homeostasis. Annu Rev Nutr 2005; 25: 215-235
  • 12 Misu H, Takamura T, Takayama H. et al. A liver-derived secretory protein, selenoprotein P, causes insulin resistance. Cell Metab 2010; 12: 483-495
  • 13 Jung TW, Choi HY, Lee SY. et al. Salsalate and adiponectin improve palmitate-induced insulin resistance via inhibition of selenoprotein p through the ampk-foxo1alpha pathway. PLoS One 2013; 8: e66529
  • 14 Mita Y, Nakayama K, Inari S. et al. Selenoprotein P-neutralizing antibodies improve insulin secretion and glucose sensitivity in type 2 diabetes mouse models. Nat Commun 2017; 8: 1658
  • 15 Lebensztejn DM, Flisiak-Jackiewicz M, Bialokoz-Kalinowska I. et al. Hepatokines and non-alcoholic fatty liver disease. Acta Biochim Pol 2016; 63: 459-467
  • 16 Yoo HJ, Choi KM. Hepatokines as a Link between obesity and cardiovascular diseases. Diabetes Metab J 2015; 39: 10-15
  • 17 Choi HY, Hwang SY, Lee CH. et al. Increased selenoprotein p levels in subjects with visceral obesity and nonalcoholic Fatty liver disease. Diabetes Metab J 2013; 37: 63-71
  • 18 Cetindagli I, Kara M, Tanoglu A. et al. Evaluation of endothelial dysfunction in patients with nonalcoholic fatty liver disease: Association of selenoprotein P with carotid intima-media thickness and endothelium-dependent vasodilation. Clin Res Hepatol Gastroenterol 2017; 41: 516-524
  • 19 di Giuseppe R, Koch M, Schlesinger S. et al. Circulating selenoprotein P levels in relation to MRI-derived body fat volumes, liver fat content, and metabolic disorders. Obesity 2017; 25: 1128-1135
  • 20 Polyzos S, Kountouras J, Papatheodorou A. et al. Adipocytokines and cytokeratin-18 in patients with nonalcoholic fatty liver disease - Introduction of CHA index. Ann Hepatol 2013; 12: 749-757
  • 21 Polyzos SA, Kountouras J, Patsiaoura K. et al. Serum homocysteine levels in patients with nonalcoholic fatty liver disease. Ann Hepatol 2012; 11: 68-76
  • 22 Kleiner DE, Brunt EM, Van NM. et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41: 1313-1321
  • 23 Matthews DR, Hosker JP, Rudenski AS. et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
  • 24 Gharipour M, Sadeghi M, Salehi M et al. Association of expression of selenoprotein P in mRNA and protein levels with metabolic syndrome in subjects with cardiovascular disease: Results of the selenegene study. J Gene Med 2017; 19:
  • 25 Hesse-Bahr K, Dreher I, Kohrle J. The influence of the cytokines Il-1beta and INFgamma on the expression of selenoproteins in the human hepatocarcinoma cell line HepG2. Biofactors 2000; 11: 83-85
  • 26 Renko K, Hofmann PJ, Stoedter M. et al. Down-regulation of the hepatic selenoprotein biosynthesis machinery impairs selenium metabolism during the acute phase response in mice. FASEB J 2009; 23: 1758-1765
  • 27 Zhang Y, Chen X. Reducing selenoprotein P expression suppresses adipocyte differentiation as a result of increased preadipocyte inflammation. Am J Physiol Endocrinol Metab 2011; 300: E77-E85
  • 28 Polyzos SA, Mantzoros CS. Adiponectin as a target for the treatment of nonalcoholic steatohepatitis with thiazolidinediones: A systematic review. Metabolism 2016; 65: 1297-1306
  • 29 Polyzos SA, Kountouras J, Zavos C. The multi-hit process and the antagonistic roles of tumor necrosis factor-alpha and adiponectin in nonalcoholic fatty liver disease. Hippokratia 2009; 13: 127
  • 30 Hybsier S, Schulz T, Wu Z. et al. Sex-specific and inter-individual differences in biomarkers of selenium status identified by a calibrated ELISA for selenoprotein P. Redox Biol 2017; 11: 403-414