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Adipokine Levels Versus Hepatic Histopathology in Bariatric Surgery Patients

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Abstract

Background

Obesity is a worldwide prevalent disease and is an underlying factor of non-alcoholic fatty liver disease (NAFLD). It has been understood as a chronic inflammatory state, being associated with the production of adipokines. The aim of this study was to analyze the levels of adipokines in the serum, visceral, and subcutaneous fat and to compare them with hepatic histopathology in morbidly obese patients.

Methods

This is a cross-sectional observational study, which analyzed the findings of liver biopsy in patients undergoing bariatric surgery and who had performed analysis of adipokines mRNA expression (adiponectin—ADIPOQ, leptin—LEP, and resistin—RETN) in subcutaneous and visceral adipose tissue and circulating adipokines in serum. Liver biopsies performed were evaluated according to Kleiner criteria.

Results

The study analyzed 25 patients undergoing bariatric surgery. The sample was composed exclusively of women. There was a predominance of NAFLD, with 21 patients (84%) with intrahepatic fat accumulation. Twelve patients presented non-alcoholic steatohepatitis (NASH). Glycated hemoglobin levels (HbA1c) were elevated in NASH patients. ADIPOQ levels were directly correlated with high-density lipoprotein (HDL) cholesterol levels and inversely correlated with triglycerides and total cholesterol. LEP levels showed an inverse relationship with the degree of steatosis, and RETN levels showed an inverse relationship with fibrosis stages.

Conclusion

Serum LEP levels were reduced in the presence of increased levels of intrahepatic fat, and serum levels of RETN were diminished in the presence of NASH. HbA1c levels were higher in the presence of NASH, indirectly reflecting insulin resistance. Moreover, ADIPOQ levels were related to blood lipid profile.

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References

  1. Lau DCW, Douketis JD, Morrison KM, et al. 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children. Can Med Assoc J. 2007;176(8):S1–13.

    Article  Google Scholar 

  2. Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34(3):274–85.

    Article  CAS  PubMed  Google Scholar 

  3. WGO Global Guidelines. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. World Gastroenterol Organ Guidel. 2012.

  4. Losekann A, Weston A, de Mattos A, et al. Non-alcoholic steatohepatitis (NASH): risk factors in morbidly obese patients. Int J Mol Sci. 2015;16(10):25552–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Losekann A, Weston AC, Carli LA, et al. Nonalcoholic fatty liver disease in severe obese patients, subjected to bariatric surgery. Arq Gastroenterol. 2013;50(4):285–9.

    Article  PubMed  Google Scholar 

  6. Rinella ME. Nonalcoholic fatty liver disease a systematic review. JAMA. 2015;169(2):170.

    Google Scholar 

  7. Frayn KN, Arner P, Yki-Jarvinen H. Fatty acid metabolism in adipose tissue, muscle and liver in health and disease. Essays Biochem. 2006;42:89–103.

    Article  CAS  PubMed  Google Scholar 

  8. Deng Y, Scherer PE. Adipokines as novel biomarkers and regulators of the metabolic syndrome. Ann N Y Acad Sci. 2010;1212:1–25.

    Article  Google Scholar 

  9. Petta S, Gastaldelli A, Rebelos E, et al. Pathophysiology of non alcoholic fatty liver disease. Int J Mol Sci. 2016;17(12):2082.

    Article  PubMed Central  Google Scholar 

  10. Li X-L, Sui J-Q, Lu L-L, et al. Gene polymorphisms associated with non-alcoholic fatty liver disease and coronary artery disease: a concise review. Lipids Health Dis Lipids in Health and Disease. 2016;15(1):53.

    Article  PubMed  Google Scholar 

  11. Jarrar MH, Baranova A, Collantes R, et al. Adipokines and cytokines in non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2008;27(5):412–21.

    Article  CAS  PubMed  Google Scholar 

  12. Abenavoli L, Peta V. Role of adipokines and cytokines in non-alcoholic fatty liver disease. Rev Recent Clin Trials. 2014;9(3):134–40.

    Article  CAS  PubMed  Google Scholar 

  13. Buechler C, Wanninger J, Neumeier M. Adiponectin, a key adipokine in obesity related liver diseases. World J Gastroenterol. 2011;17(23):2801–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Stojsavljević S, Gomerčić Palčić M, Virović Jukić L, et al. Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20(48):18070–91.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Tsochatzis EA, Papatheodoridis GV, Archimandritis AJ. Adipokines in nonalcoholic steatohepatitis: from pathogenesis to implications in diagnosis and therapy. Mediat Inflamm. 2009;2009:831670.

    Article  Google Scholar 

  16. Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313–21.

    Article  PubMed  Google Scholar 

  17. Targher G, Bertolini L, Rodella S, et al. Associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease. Clin Endocrinol. 2006;64(6):679–83.

    Article  CAS  Google Scholar 

  18. Karbowska J, Kochan Z. Role of adiponectin in the regulation of carbohydrate and lipid metabolism. In: J Physiol Pharmacol. 2006. p. 103–13.

  19. Lee B, Shao J. Adiponectin and lipid metabolism in skeletal muscle. Acta Pharm Sin B. 2012;2(4):335–40.

    Article  CAS  Google Scholar 

  20. Baratta R, Amato S, Degano C, Farina MG, Patanè G, Vigneri R, et al. Adiponectin relationship with lipid metabolism is independent of body fat mass: evidence from both cross-sectional and intervention studies. In: J Clin Endocrinol Metabol. 2004. p. 2665–71.

  21. Bugianesi E, Pagotto U, Manini R, et al. Plasma adiponectin in nonalcoholic fatty liver is related to hepatic insulin resistance and hepatic fat content, not to liver disease severity. J Clin Endocrinol Metab. 2005;90(6):3498–504.

    Article  CAS  PubMed  Google Scholar 

  22. Pagano C, Soardo G, Esposito W, et al. Plasma adiponectin is decreased in nonalcoholic fatty liver disease. Eur J Endocrinol. 2005;152(1):113–8.

    Article  CAS  PubMed  Google Scholar 

  23. Polyzos SA, Mantzoros CS. Adiponectin as a target for the treatment of nonalcoholic steatohepatitis with thiazolidinediones: a systematic review. Metabolism. 2016;65(9):1297–306.

    Article  CAS  PubMed  Google Scholar 

  24. Spranger J, Kroke A, Möhlig M, et al. Adiponectin and protection against type 2 diabetes mellitus. Lancet. 2003;361(9353):226–8.

    Article  CAS  PubMed  Google Scholar 

  25. Argentou M, Tiniakos DG, Karanikolas M, et al. Adipokine serum levels are related to liver histology in severely obese patients undergoing bariatric surgery. Obes Surg. 2009;19(9):1313–23.

    Article  PubMed  Google Scholar 

  26. Abenavoli L, DI Renzo L, Guzzi PH, et al. Non-alcoholic fatty liver disease severity, central fat mass and adinopectin: a close relationship. Clujul Med. 2015;88(4):489–93.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Baranova A, Gowder SJ, Schlauch K, et al. Gene expression of leptin, resistin, and adiponectin in the white adipose tissue of obese patients with non-alcoholic fatty liver disease and insulin resistance. Obes Surg. 2006;16(9):1118–25.

    Article  PubMed  Google Scholar 

  28. Jamali R, Arj A, Razavizade M, et al. Prediction of nonalcoholic fatty liver disease via a novel panel of serum adipokines. Medicine (Baltimore). 2016a;95(5):e2630.

    Article  CAS  Google Scholar 

  29. Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996;334(5):292–5.

    Article  CAS  PubMed  Google Scholar 

  30. Lönnqvist F, Arner P, Nordfors L, et al. Overexpression of the obese (Ob) gene in adipose tissue of human obese subjects. Nat Med. 1995;1(9):950–3.

    Article  PubMed  Google Scholar 

  31. Tsochatzis E, Papatheodoridis GV, Archimandritis AJ. The evolving role of leptin and adiponectin in chronic liver diseases. Am J Gastroenterol. 2006;101(11):2629–40.

    Article  CAS  PubMed  Google Scholar 

  32. Ikejima K, Takei Y, Honda H, et al. Leptin receptor-mediated signaling regulates hepatic fibrogenesis and remodeling of extracellular matrix in the rat. Gastroenterology. 2002;122(5):1399–410.

    Article  CAS  PubMed  Google Scholar 

  33. Ikejima K, Honda H, Yoshikawa M, et al. Leptin augments inflammatory and profibrogenic responses in the murine liver induced by hepatotoxic chemicals. Hepatology. 2001;34(2):288–97.

    Article  CAS  PubMed  Google Scholar 

  34. Chitturi S, Farrell G, Frost L, et al. Serum leptin in NASH correlates with hepatic steatosis but not fibrosis: a manifestation of lipotoxicity? Hepatology. 2002;36(2):403–9.

    Article  CAS  PubMed  Google Scholar 

  35. Tsochatzis E, Papatheodoridis GV, Hadziyannis E, et al. Serum adipokine levels in chronic liver diseases: association of resistin levels with fibrosis severity. Scand J Gastroenterol. 2008;43(9):1128–36.

    Article  CAS  PubMed  Google Scholar 

  36. Polyzos SA, Aronis KN, Kountouras J, et al. Circulating leptin in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Diabetologia. 2016;59(1):30–43.

    Article  CAS  PubMed  Google Scholar 

  37. Polyzos SA, Kountouras J, Mantzoros CS. Leptin in nonalcoholic fatty liver disease: a narrative review. Metab Clin Exp. 2015;64:60–78.

    Article  CAS  PubMed  Google Scholar 

  38. Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes. Nature. 2001;409(6818):307–12.

    Article  CAS  PubMed  Google Scholar 

  39. De Luis DA, Terroba MC, Cuellar L, et al. Resistin levels in morbid obese patients following the biliopancreatic diversion surgery. Horm Metab Res. 2011;43(3):205–8.

    Article  CAS  PubMed  Google Scholar 

  40. Aller R, de Luis D, Fernandez L, et al. Influence of insulin resistance and adipokines in the grade of steatosis of nonalcoholic fatty liver disease. Dig Dis Sci. 2008;53(4):1088–92.

    Article  CAS  PubMed  Google Scholar 

  41. Pagano C, Soardo G, Pilon C, et al. Increased serum resistin in nonalcoholic fatty liver disease is related to liver disease severity and not to insulin resistance. J Clin Endocrinol Metab. 2006;91(3):1081–6.

    Article  CAS  PubMed  Google Scholar 

  42. Senates E, Çolak Y, Yesil A, et al. Circulating resistin is elevated in patients with non-alcoholic fatty liver disease and its associated with steatosis, portal inflammation, insulin resistance and no alcoholic steatohepatitis scores. Minerva Med. 2012;53(9):1689–99.

    Google Scholar 

  43. Cengiz C, Ardicoglu Y, Bulut S, et al. Serum retinol-binding protein 4 in patients with nonalcoholic fatty liver disease: does it have a significant impact on pathogenesis? Eur J Gastroenterol Hepatol. 2010;22(7):813–9.

    Article  CAS  PubMed  Google Scholar 

  44. Jamali R, Razavizade M, Arj A, et al. Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease. World J Gastroenterol. 2016b;22(21):5096–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Perseghin G, Lattuada G, De Cobelli F, et al. Serum resistin and hepatic fat content in nondiabetic individuals. J Clin Endocrinol Metab. 2006;91(12):5122–5.

    Article  CAS  PubMed  Google Scholar 

  46. Bekaert M, Verhelst X, Geerts A, et al. Association of recently described adipokines with liver histology in biopsy-proven non-alcoholic fatty liver disease: a systematic review. Obes Rev. 2016;17(1):68–80.

    Article  CAS  PubMed  Google Scholar 

  47. Samaras K, Botelho NK, Chisholm DJ, et al. Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes. Obesity (silver spring). Nat Publ Group. 2010;18(5):884–9.

    CAS  Google Scholar 

  48. Blüher M, Fasshauer M, Kralisch S, et al. Regulation of adiponectin receptor R1 and R2 gene expression in adipocytes of C57BL/6 mice. Biochem Biophys Res Commun. 2005;329(3):1127–32.

    Article  PubMed  Google Scholar 

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Correspondence to Rafael Bergesch D’Incao.

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The authors declare that they have no conflict of interest.

Ethical Statement

This study was submitted to and approved by the Research Ethics Committee of Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA) and of Hospital Nossa Senhora da Conceição (HNSC). All participants signed an inform consent form authorizing adipose tissue and blood sample collection previous to surgery procedures and their storage for further studies. These samples were collected for a previous larger study, and their utilization in the present study and collection of information from routine liver biopsies performed during surgery from their medical records was authorized by both institutions.

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D’Incao, R.B., Tovo, C.V., Mattevi, V.S. et al. Adipokine Levels Versus Hepatic Histopathology in Bariatric Surgery Patients. OBES SURG 27, 2151–2158 (2017). https://doi.org/10.1007/s11695-017-2627-4

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