Hepatology International

, Volume 4, Issue 4, pp 767–774 | Cite as

Study of adiponectin in chronic liver disease and cholestasis

  • Tary A. Salman
  • Naglaa Allam
  • Gasser I. Azab
  • Ahmed A. Shaarawy
  • Mona M. Hassouna
  • Omkolsoum M. El-haddad
Original Article

Abstract

Purpose

Adiponectin is an adipocytokine suggested to have a hepatoprotective effect. To date, little information is available in the literature regarding changes in serum adiponectin levels in cirrhosis and cholestasis and the associated metabolic disturbances. In order to elucidate the role of adiponectin in chronic liver disease our aim was to determine serum adiponectin in patients with different grades of cirrhosis and cholestasis and to correlate it with markers of liver injury, inflammation and cholestasis. We also aimed to correlate adiponectin with markers of metabolic syndrome such as body mass index and insulin resistance.

Methods

Forty patients with cirrhosis; 30 patients with cirrhosis and cholestasis; and 20 matched controls were studied. They were subjected to clinical assessment, laboratory investigations: serum bilirubin, ALT, AST, alkaline phosphatase, GGT, albumin, C-reactive protein, prothrombin activity, fasting blood sugar, insulin. HOMA index was calculated. Abdominal ultrasonography and upper GI endoscopy were performed.

Results

Adiponectin was elevated in patients with cirrhosis and cirrhosis/cholestasis and was significantly higher in Child A and B. Adiponectin showed correlation with liver cell injury, marker of inflammation, synthetic liver function and markers of cholestasis. Adiponectin did not correlate with complications of cirrhosis as ascites and esophageal varices nor did it correlate with BMI or HOMA.

Conclusions

Adiponectin is elevated in cirrhosis and shows correlation with degree of hepatocellular injury and cholestasis. Finally, adiponectin levels in cirrhosis do not correlate with parameters of body composition or metabolism but exclusively with reduced liver function.

Keywords

Serum adiponectin Cirrhosis and cholestasis 

References

  1. 1.
    Sennello JA, Fayad R, Morris AM, Eckel RH, Asilmaz E, Montez J, Friedman JM, Dinarello CA, Fantuzz G. Regulation of T cell-mediated hepatic inflammation by adiponectin and leptin. Endocrinology 2005;146(5):2157–2164CrossRefPubMedGoogle Scholar
  2. 2.
    Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y, Matsuzawa Y. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 2000;96:1723–1732PubMedGoogle Scholar
  3. 3.
    Berg AH, Combs TP, Du XL, Brownlee M, Scherer P. The adipocyte secreted protein Acrp30 enhances hepatic insulin action. Nat Med 2001;7:947–953CrossRefPubMedGoogle Scholar
  4. 4.
    Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003;423:762–769CrossRefPubMedGoogle Scholar
  5. 5.
    Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, Ohashi K, Sakai N, Shimomura I, Kobayashi H, Terasaka N, Inaba T, Funahashi T, Matsuzawa Y. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 2002;106:2767–2770CrossRefPubMedGoogle Scholar
  6. 6.
    Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 1999;100:2473–2476PubMedGoogle Scholar
  7. 7.
    Wolf AM, Wolf D, Rumpold H, Enrich B, Tilg H. Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochem Biophys Res Commun 2004;323:630–635CrossRefPubMedGoogle Scholar
  8. 8.
    Yamamoto K, Kiyohara T, Murayama Y, Kihara S, Okamoto Y, Funahashi T, Ito T, Nezu R, Tsutsui S, Miyagawa J-I, Tamura S, Matsuzawa Y, Shimomura I, Shinomura Y. Production of adiponectin, an anti-inflammatory protein, in mesenteric adipose tissue in Crohn’s disease. Gut 2005;54:789–796CrossRefPubMedGoogle Scholar
  9. 9.
    Tsuchida A, Yamauchi T, Ito Y, Hada Y, Maki T, Takekawa S, Kamon J, Kobayashi M, Suzuki R, Hara K, Kubota N, Terauchi Y, Frogue PH, Nakae J, Kasuga M, Accili D, Tobe K, Ueki K, Nagai R, Kadowaki T. Insulin/Foxo1 pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity. J Biol Chem 2004;279:30817–30822CrossRefPubMedGoogle Scholar
  10. 10.
    Jonsson JR, Moschen AR, Hickman IJ, Richardson MM, Kaser S, Clouston AD, Powell EE, Tilg H. Adiponectin and its receptors in patients with chronic hepatitis C. J Hepatol 2005;43:929–936CrossRefPubMedGoogle Scholar
  11. 11.
    Pagano C, Soardo G, Esposito W, Fallo F, Basan L, Donnini D, Federspil G, Sechi LA, Vettor R. Plasma adiponectin is decreased in nonalcoholic fatty liver disease. Eur J Endocrinol 2005;152:113–118CrossRefPubMedGoogle Scholar
  12. 12.
    Beltowski J. Adiponectin and resistin: new hormones of white adipose tissue. Med Sci Monit 2003;9:RA55–RA61PubMedGoogle Scholar
  13. 13.
    Vandivier RW, Ogden CA, Fadok VA, Hoffmann PR, Brown KK, Botto M, Walport MJ, Fisher JH, Henson PM, Greene KE. Role of surfactant proteins A, D, and C1q in the clearance of apoptotic cells in vivo and in vitro: calreticulin and CD91 as a common collectin receptor complex. J Immunol 2002;169:3978–3986PubMedGoogle Scholar
  14. 14.
    Diez JJ, Iglesias P. The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur J Endocrinol 2003;148:293–300CrossRefPubMedGoogle Scholar
  15. 15.
    Chinetti G, Zawadski C, Fruchart JC, Staels B. Expression of adiponectin receptors in human macrophages and regulation by agonists of the nuclear receptors PPARα, PPARγ and LXR. Biochem Biophys Res Commun 2004;314:151–158CrossRefPubMedGoogle Scholar
  16. 16.
    Rakatzi I, Mueller H, Ritzeler O, Tennagels N, Eckel J. Adiponectin counteracts cytokine- and fatty acid-induced apoptosis in the pancreatic β-cell line INS-1. Diabetologia 2004;47:249–258CrossRefPubMedGoogle Scholar
  17. 17.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–419CrossRefPubMedGoogle Scholar
  18. 18.
    Tietge UJ, Böker KH, Manns MP, Bahr MJ. Elevated circulating adiponectin levels in liver cirrhosis are associated with reduced liver function and altered hepatic hemodynamics. Am J Physiol Endocrinol Metab 2004;87(1):82–89CrossRefGoogle Scholar
  19. 19.
    Hui CK, Zhang HY, Lee NP, Chan W, Yueng YH, Leung KW. Serum adiponectin is increased in advancing liver fibrosis and declines with reduction in fibrosis in chronic hepatitis B. J Hepatol 2007;47:191–202CrossRefPubMedGoogle Scholar
  20. 20.
    Sohara N, Takagi H, Kakizaki S, Sato K, Mori M. Elevated plasma adiponectin concentrations in patients with liver cirrhosis correlate with plasma insulin levels. Liver Int 2005;25(1):28–32CrossRefPubMedGoogle Scholar
  21. 21.
    Xu A, Wang Y, Keshaw H, Xu LY, Lam KS, Cooper GJ. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest 2003;112:91–100PubMedGoogle Scholar
  22. 22.
    Masaki T, Chiba S, Tatsukawa T, Noguchi H, Seike M, Yoshimatsu H. Adiponectin protects LPS-induced liver injury through modulation of TNF-α in KK-Ay obese mice. Hepatology 2004;40:177–84CrossRefPubMedGoogle Scholar
  23. 23.
    Kaser S, Moschen A, Kaser A, Ludwiczek O, Ebenbichler CF, Vogel W, Jaschke W, Patsch JR, Tilg H. Circulating adiponectin reflects severity of liver disease but not insulin sensitivity in liver cirrhosis. J Intern Med 2005;258(3):274–280CrossRefPubMedGoogle Scholar
  24. 24.
    Yoda-Murakami M, Taniguchi M, Takahashi K, Kawamata S, Saito K, Choi-Miura NH, Tomita M. Change in expression of GBP28/adiponectin in carbon tetrachloride-administrated mouse liver. Biochem Biophys Res Commun 2001;285:372–377CrossRefPubMedGoogle Scholar
  25. 25.
    Ding X, Saxena NK, Lin S, Xu A, Srinivasan S, Anania FA. The roles of leptin and adiponectin. A novel paradigm in adipocytokine regulation of liver fibrosis and stellate cell biology. Am J Pathol 2005;166:1655–1669PubMedGoogle Scholar
  26. 26.
    Liu CJ, Chen PJ, Lai MY, Lui CH, Chen CL, Kao JH, Chen DS. High serum adiponectin correlates with advanced liver disease in patients with chronic hepatitis B virus infection. Hepatol Int 2009;3:364–370CrossRefPubMedGoogle Scholar
  27. 27.
    Petit JM, Minello A, Jooste V, Bour JB, Galland F, Duvillard L, Verges B, Olsson NO, Hillon GP. Decreased plasma adiponectin concentrations are closely related to steatosis in HCV-infected patients. J Clin Endocrinol Metabol 2005;10:1266Google Scholar
  28. 28.
    Tacke F, Wüstefeld T, Horn R, Luedde T, Rao AS, Manns MP, Trautwein C, Brabant G. High adiponectin in chronic liver disease and cholestasis suggests biliary route of adiponectin excretion in vivo. J Hepatol 2005;42:666–673CrossRefPubMedGoogle Scholar
  29. 29.
    Matsushita K, Yatsuya H, Tamakoshi K, Wada K, Otsuka R, Zhang H, Sugiura K, Kondo T, Murohara T, Toyoshima H. Inverse association between adiponectin and C-reactive protein in substantially healthy Japanese men. Atherosclerosis 2006;188(1):184–189CrossRefPubMedGoogle Scholar
  30. 30.
    Takemura Y, Ouchi N, Shibata R, Aprahamian T, Kirber MT, Summer RS, Kihara S, Walsh K. Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies. J Clin Invest 2007;117:375–386CrossRefPubMedGoogle Scholar
  31. 31.
    Bota DP, Van Nuffelen M, Zakariah A, Vincent JL. Serum levels of C-reactive protein and procalcitonin in critically ill patients with cirrhosis of the liver. J Lab Clin Med 2005;146(6):347–351CrossRefPubMedGoogle Scholar
  32. 32.
    Kazumi T, Kawaguchi A, Hirano T, Yoshino G. Serum alanine aminotransferase is associated with serum adiponectin, C-reactive protein and apolipoprotein B in young healthy men. Horm Metab Res 2006;38(2):119–124CrossRefPubMedGoogle Scholar
  33. 33.
    Chudek J, Adamczak M, Karkoszka H, Budzinski G, Ignacy W, Funahashi T, Matsuzawa Y, Cierpka L, Kokot F, Wiecek A. Plasma adiponectin concentration before and after successful kidney transplantation. Transplant Proc 2003;35:2186–2189CrossRefPubMedGoogle Scholar
  34. 34.
    Koshimura J, Fujita H, Narita T, Shimotomai T, Hosoba M, Yoshioka N, Kakei M, Fujishima H, Ito S. Urinary adiponectin excretion is increased in patients with overt diabetic nephropathy. Biochem Biophys Res Commun 2004;316:165–169CrossRefPubMedGoogle Scholar
  35. 35.
    Floreani A, Variola A, Niro G, Premoli A, Baldo V, Gambino R, Musso G, Cassader M, Bo S, Ferrara F, Caroli D, Rizzotto ER, Durazzo M. Plasma adiponectin levels in primary biliary cirrhosis: a novel perspective for link between hypercholesterolemia and protection against atherosclerosis. Am J Gastroenterol 2008;103(8):1959–1965CrossRefPubMedGoogle Scholar
  36. 36.
    Perseghin G, Mazzaferro V, Benedini S, Pulvirenti A, Coppa J, Regalia E, Luzi L. Resting energy expenditure in diabetic and nondiabetic patients with liver cirrhosis: relation with insulin sensitivity and effect of liver transplantation and immunosuppressive therapy. Am J Clin Nutr 2002;76(3):541–548PubMedGoogle Scholar
  37. 37.
    Salmenniemi U, Zacharova J, Ruotsalainen E, Vauhkonen I, Pihlajamäki J, Kainulainen S, Punnonen K, Laakso M. Association of adiponectin level and variants in the adiponectin gene with glucose metabolism, energy expenditure, and cytokines in offspring of type 2 diabetic patients. J Clin Endocrinol Metabol 2005;90(7):4216–4223CrossRefGoogle Scholar
  38. 38.
    Whitehead JP, Richards AA, Hickman IJ, Macdonald GA, Prins JB. Adiponectin—a key adipokine in the metabolic syndrome. Diabetes Obes Metab 2006;8(3):264–280CrossRefPubMedGoogle Scholar
  39. 39.
    Petrides AS, Strohmeyer G, DeFronzo RA. Insulin resistance in liver cirrhosis and portal hypertension. Prog Liver Dis 1992;10:311–328PubMedGoogle Scholar
  40. 40.
    Record CO. Glucose and insulin metabolism in cirrhosis. Adv Exp Med Biol 1997;420:229–233Google Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2010

Authors and Affiliations

  • Tary A. Salman
    • 1
  • Naglaa Allam
    • 1
  • Gasser I. Azab
    • 1
  • Ahmed A. Shaarawy
    • 2
  • Mona M. Hassouna
    • 2
  • Omkolsoum M. El-haddad
    • 1
  1. 1.Hepatology, National Liver InstituteMenofeya UniversityShebeen El-KomEgypt
  2. 2.Clinical Pathology, National Liver InstituteMenofeya UniversityShebeen El-KomEgypt

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