Combined Adiponectin Deficiency and Resistance in Obese Patients: Can It Solve Part of the Puzzle in Nonalcoholic Steatohepatitis

Ahmed Salman; Mona Hegazy; Soheir AbdElfadl

doi:10.3889/oamjms.2015.057

Authors

Ahmed Salman Faculty of Medicine, Cairo University, Internal Medicine, Cairo
Mona Hegazy Faculty of Medicine, Cairo University, Internal Medicine, Cairo
Soheir AbdElfadl Faculty of Medicine, Cairo University, Internal Medicine, Cairo

DOI:

https://doi.org/10.3889/oamjms.2015.057

Keywords:

Combined adiponectin deficiency and resistance in obese patients, can it solve part of the puzzle in NASH

Abstract

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease, nonalcoholic steatohepatitis (NASH) and fibrosis in obese patients identifies the risk group with increased incidence of liver-related deaths.

AIM: To clarify the role of serum adiponectin and its receptor liver gene expression in the progression of liver damage in NAFLD.

METHODS: Fifty four (54) obese patients with NAFLD preliminary diagnosed by liver ultra-sound were recruited. Full medical history, anthropometric measurement, biochemical studies, serum adiponectin level, liver biopsy for histological examination and NAS score to identify NASH patients, and assessment of adiponectin receptor gene expression by RT-PCR, were conducted for each patients. Fifteen ages matched average weight healthy adult had been chosen as a control for serum adiponectin level.

RESULTS: According to NAS score, patients were divided into non- NASH (8 patients), and NASH (46 patients). Serum adiponectin level was significantly lower in NAFLD patients compared to normal participants (p < 0.004). Serum adiponectin level was lower in NASH patients (4.437 Â± 2.569 ng/dl in NASH vs. 5.138 Â± 2.841 ng/dl in non-NASH). Adiponectin receptor liver gene expression was lower in NASH patients (0.8459 Â± 0.4671 vs. 1.0688 Â± 0.3965 in non-NASH).

CONCLUSION: Both adiponectin deficiency and resistance had a role in progression of simple liver steatosis to severe injury in obese patients.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Ludwig J, Viggiano TR, McGill DB, Barge J. Nonalcoholic steatohepatitis: mayo clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980; 55: 434-8.

Vuppalanchi R, Chalasani N. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: selected practical issues in their evaluation and management. Hepatology. 2009; 49: 306-17. DOI: https://doi.org/10.1002/hep.22603

De Alwis NM, Day CP. Non-alcoholic fatty liver disease: the mist gradually clears. J Hepatol. 2008; 48 Suppl. 1: S104-12. DOI: https://doi.org/10.1016/j.jhep.2008.01.009

Mathurin P, Hollebecque A, Arnalsteen L, Buob D, Leteurtre E, Caiazzo R, et al. Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. Gastroenterology. 2009; 137: 532-40. DOI: https://doi.org/10.1053/j.gastro.2009.04.052

Admaska A, Nikolajuk A, Karczewska-Kupczewska M , Kowalska I, Otziomek E, GÃ³rska M, et al. Relationships between serum adiponectin, soluble TNF-Î± receptors, glucose and lipid oxidation in lean and obese subjects. Acta.Diabetol. 2012; 49: 17-24. DOI: https://doi.org/10.1007/s00592-010-0252-y

Isabelle B Bauche, Samira Ait El Mkadem, Anne-Marie Pottier, Maximin Senou, Marie-Christine Many, RenÃ© Rezsohazy, et al"Over-expression of adiponectin targeted to adipose tissue in transgenic Mice: impaired adipocyte differentiation". Endocrinology. 2007; 148: 1539-49. DOI: https://doi.org/10.1210/en.2006-0838

Wang Y, Lam KS, Chan L. Post-translational modifications of the four conserved lysine residues within the collagenous domain of adiponectin are required for the formation of its high molecular weight oligomeric complex. J. Biol Chem. 2006; 281: 16391-400. DOI: https://doi.org/10.1074/jbc.M513907200

Kadowaki T, Yamauchi T, Kubota N. The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS. FEBS Lett. 2008; 582: 74-80. DOI: https://doi.org/10.1016/j.febslet.2007.11.070

Toshimasa Yamauchi, Yasunori Nio, Toshiyuki Maki, Masaki Kobayashi, Takeshi Takazawa, Masato Iwabu, et al. Targeted disruption of Adipo R1 and Adipo R2 causes abrogation of adiponectin binding and metabolic actions. Nat Med. 2007; 13: 332-9. DOI: https://doi.org/10.1038/nm1557

Atsushi Tsuchida, Toshimasa Yamauchi, Yusuke Ito, Yusuke Hada, Toshiyuki Maki, Sato Takekawa, et al. Insulin/Foxo 1 pathway regulates expression levels of adiponectin receptors and Adiponectin sensitivity. J Biol Chem.2004; 279: 30817-22. DOI: https://doi.org/10.1074/jbc.M402367200

Mingyan Zhou, Aimin Xu, Paul K H Tam, Karen S L Lam, Lawrence Chan, Ruby L C Hoo, et al. Mitochondrial dysfunction contributes to the increased vulnerabilities of adiponectin knockout mice to liver injury. Hepatology. 2008; 48: 1087-96. DOI: https://doi.org/10.1002/hep.22444

Claudio Ricci, Renata Longo, Eugenio Gioulis, Marco Bosco, Piero Pollesello Flura Masutti, et al. Noninvasive in vivo quantitative assessment of fat in human liver. J Hepatol. 1997; 27: 108-13. DOI: https://doi.org/10.1016/S0168-8278(97)80288-7

David E. Kleiner, Elizabeth M. Brunt, Mark Van Natta, Cynthia Behling, Melissa J. Contos, Oscar W. Cummings, et al. Design and validation of a histoloical scoring system for nonalcoholic fatty liver disease. Hepatology. 2005; 41:1313-21. DOI: https://doi.org/10.1002/hep.20701

Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steathepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999; 94: 2467-74. DOI: https://doi.org/10.1111/j.1572-0241.1999.01377.x

VanGuildre HD, Vrana KE, Ferrman W. Twenty-five years of quantitative PCR for gene expression analysis. Biotechniques. 2008; 44: 619-26. DOI: https://doi.org/10.2144/000112776

Giulio Marchesini, Simona Moscatiello, Federica Agostini, Nicola Villanova, Davide Festi. Treatment of non-alcoholic fatty liver disease with focus on emerging drugs. Expert Opin Emerg Drugs. 2011; 1: 121-36. DOI: https://doi.org/10.1517/14728214.2011.531700

Torres DM and Harrison SA. Diagnosis and therapy of nonalcoholic steatohepatitis. Gastroenterology. 2008; 134: 1682-98. DOI: https://doi.org/10.1053/j.gastro.2008.02.077

Ling-Ling Jiang, Lin Li, Xiao-Fei Hong, You-Ming Li, Bing-Ling Zhang. Patients with non alcoholic fatty liver disease display increased serum resistin levels and decreased adiponectin levels. Eur J Gastoenterol Hepatol. 2009; 21: 662-6. DOI: https://doi.org/10.1097/MEG.0b013e328317f4b5

Coppola A, Marfella R, Coppola L, Tagliamonte E, Fontana D, Liguori E, Cirillo T, Cafiero M, Natale S, Astarita C. Effect of weight loss on coronary circulation and adiponectin levels in obese women. Int J Cardiol. 2009;134(3):414-6. DOI: https://doi.org/10.1016/j.ijcard.2007.12.087

Baranova A, Gowder SJ, Schlauch K, Elariny H, Collantes R, Afendy A, Ong JP, Goodman Z, Chandhoke V, Younossi ZM. 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. DOI: https://doi.org/10.1381/096089206778392149

Arvaniti VA, Thomopoulos KC, Tsamandas A, Makri M, Psyrogiannis A, Vafiadis G, Assimakopoulos SF, Labropoulou-Karatza C. Serum adiponectin levels in different types of non alcoholic liver disease. Correlation with steatosis, necroinflammation and fibrosis. Acta Gastroenterol Belg. 2008;71(4):355-60.

Polyzos SA, Toulis KA, Goulis DG, Zavos C, Kountouras J. Serum total adiponectin in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Metabolism. 2011;60(3):313-26. DOI: https://doi.org/10.1016/j.metabol.2010.09.003

Savvidou S, Hytiroglou P, Orfanou-Koumerkeridou H, Panderis A, Frantzoulis P, Goulis J. Low serum adiponectin levels are predictive of advanced hepatic fibrosis in patients with NAFLD. J Clin Gastroenterol. 2009;43(8):765-72. DOI: https://doi.org/10.1097/MCG.0b013e31819e9048

Vuppalanchi R, Marri S, Kolwankar D, Considine RV, Chalasani N. Is adiponectin involved in the pathogenesis of nonalcoholic steatohepatitis? A preliminary human study. J Clin Gastroenterol. 2005; 39: 237-42. DOI: https://doi.org/10.1097/01.mcg.0000152747.79773.2f

Ma H, Gomez V, Lu L, Yang X, Wu X, Xiao SY. Expression of adiponectin and its receptors in livers of morbidly obese patients with non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2009;24(2):233-7. DOI: https://doi.org/10.1111/j.1440-1746.2008.05548.x

Bonnard C, Durand A, Vidal H, Rieusset J. Changes in adiponectin, its receptors and AMPK activity in tissues of diet-induced diabetic mice. Diabetes Metab. 2008; 34: 52-61. DOI: https://doi.org/10.1016/j.diabet.2007.09.006

Matschinsky FM, Magnuson MA, Zelent D, Jetton TL, Doliba N, Han Y, et al.The network of glucokinase-expression cells in glucose homeostasis and the potential pf glukoinase activators for diabetes therapy. Diabetes. 2006; 55: 1-12. DOI: https://doi.org/10.2337/diabetes.55.01.06.db05-0926

Kamada Y, Takehara T, Hayashi N. Adipocytokines and liver disease. J Gastroenterology. 2008; 43: 811-22. DOI: https://doi.org/10.1007/s00535-008-2213-6