Skip to main content

Advertisement

SpringerLink
Log in

Alterations in Serum Leptin in Chronic Liver Disease

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The role of leptin in anorexia associated with liver cirrhosis remains controversial. The aim of this study was to quantify the serum leptin level in patients with hepatocellular or cholestatic liver disease and to assess its relationship with serum insulin, body mass index, and serum lipoproteins. The study population included 30 women, 15 with chronic hepatocellular liver disease and 15 with primary biliary cirrhosis; severity of disease was determined by Child-Pugh and histological criteria, respectively. Ten healthy, age-matched women served as controls. Levels of serum leptin and insulin were determined by radioimmunoassay. Mean serum leptin level was significantly lower in the primary biliary cirrhosis group compared to both the control (P ≤ 0.05) and the hepatocellular groups (P ≤ 0.05). Serum leptin level strongly correlated with body mass index in the hepatocellular group (P < 0.0001) and the controls (P < 0.001), but not in the primary biliary cirrhosis group; it showed no correlation with severity of liver disease. A positive correlation was found between serum leptin and serum cholesterol (P = 0.02), low density lipoprotein (P = 0.01), and triglycerides (P = 0.04) in the hepatocellular group and in the controls between serum leptin and serum high density lipoproteins (P = 0.01). Serum leptin is low in patients with primary biliary cirrhosis. The combined findings of normal insulin response less insulin resistance, and lower serum leptin level in primary biliary cirrhosis compared to hepatocellular liver disease may indicate that serum leptin is merely a passive marker and not a cause of anorexia in liver disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F: Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269:540–543, 1995

    Google Scholar 

  2. Zhang Y, Proenca R, Maffei M, Barome M, Leopold L, Friedman JM: Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432, 1994

    Google Scholar 

  3. Friedman JM: Leptin, leptin receptors and the control of body weight. Nutr Rev 56:S38–S46, 1997

    Google Scholar 

  4. Tartaglia LA: The leptin receptor. J Biol Chem 272:6093–6096, 1997

    Google Scholar 

  5. Kennedy A, Gettys TW, Watson P, Wallace P, Ganaway E, Pan Q, Garvey WT: The metabolic significance of leptin in humans: Gender-based differences in relationship in adiposity, insulin sensitivity and energy expenditure. J Clin Endocrinol Metab 82:1293–1300, 1997

    Google Scholar 

  6. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro JF: Serum immunoreactive-leptin concentrations in normal weight and obese humans. N Engl J Med 334:292–294, 1996

    Google Scholar 

  7. Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, Sewter CP, Digby JE, Mohammed SN, Hurst JA, Cheethan CH, Earley AR, Barnett AH, Prins JB, O'Rahilly S: Congenital leptin deficiency is associated with severe earlyonset obesity in humans. Nature 387:903–908, 1997

    Google Scholar 

  8. Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte JM, Basdevant A, Bougneres P, Lebouc Y, Froguel P, Guy-Grand B: A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392:398–401, 1998

    Google Scholar 

  9. Friedman JM: Leptin, leptin receptors and the control of body weight. Eur J Med Res 2:7–13, 1997

    Google Scholar 

  10. Jhangiani SS, Agarwal N, Holmes R, Cayten CG, Pitchumoni CS: Energy expenditure in chronic alcoholics with and without liver disease. Am J Clin Nutr 44:323–329, 1986

    Google Scholar 

  11. Muller MJ, Lautz HU, Plogmann B, Burger M, Korber J, Schmidt FW: Energy expenditure and substrate oxidation in patients with cirrhosis: The impact of cause, clinical staging and nutritional state. Hepatology 15:782–797, 1992

    Google Scholar 

  12. Grunfeld C, Zhao C, Fuller J, Pollock A, Moser A, Friedman J, Feingold KR: Endotoxin and cytokines induce expression of leptin, the ob gene product in hamsters. A role for leptin in the anorexia of infection. J Clin Invest 97:2152–2157, 1996

    Google Scholar 

  13. Merabet E, Dagogo-Jack S, Coyne DW, Klein S, Santiago JV, Hmiel SP, Landt M: Increased plasma leptin concentration in end-stage renal disease. J Clin Endocrinol 82:847–850, 1997

    Google Scholar 

  14. Shimizu H, Kakizaki S, Tsuchiya T, Nagamine T, Takagi H, Takayama H, Kobayashi I, Mori M: An increase of circulating leptin in patients with liver cirrhosis. Int J Obes Relat Metab Disord 22(12):1234–1238, 1998

    Google Scholar 

  15. Henriksen JH, Holst JJ, Moller S, Brinch K, Bendtsen F: Increased circulating leptin in alcoholic cirrhosis: Relation to release and disposal. Hepatology 29:1818–1824, 1999

    Google Scholar 

  16. McCullough AJ, Bugianesi E, Marchensini G, Kalhan SC: Gender-dependent alterations in serum leptin in alcoholic cirrhosis. Gastroenterology 115:947–953, 1998

    Google Scholar 

  17. Dua A, Hennes MI, Hoffmann RG, Maas DL, Krakower GR, Sonnenberg GE, Kissebah AH: Leptin a significant indicator of total body fat but not of visceral fat and insulin insensitivity in African women. Diabetes 45:1635–1637, 1996

    Google Scholar 

  18. Grinspoon S, Gulick T, Askari H, Landt M, Lee K, Anderson E, Ma Z. Vignati L, Bowsher R, Herzog D, Klibanski A: Serum leptin in women with anorexia nervosa. J Clin Endocrinol 81:3861–3863, 1996

    Google Scholar 

  19. Testa R, Franceschini R, Giannini E, Cataldi A, Botta F, Fasoli A, Tenerelli P, Rolandi E, Barreca T: Serum leptin levels in patients with viral chronic hepatitis or liver cirrhosis. J Hepatol 33:33–37, 2000

    Google Scholar 

  20. Greco AV, Mingrone G, Favuzzi A, Capristo E, Gniuli D, Addolorato G, Brunani A, Cavagnin F, Gasbarrini G: Serum leptin levels in post-hepatitis liver cirrhosis. J Hepatol 33:38–42, 2000

    Google Scholar 

  21. Roberts GA. Holt RG, Ghatei MA, Baker AJ, Bloom SR, Miell JP: Serum leptin and insulin in pediatric end-stage liver disease and following successful orthotopic liver transplantation. Clin Endocrinol Oxf 48:401–406, 1998

    Google Scholar 

  22. Pugh RNH, Murray-Lyom IM, Dawson JL: Transaction of oesophagus for bleeding oesophagus varices. Br J Surg 60:646–649, 1973

    Google Scholar 

  23. Dickson ER, Fleming TR, Wiesner RH, Baldus WP, Fleming CR, Ludwig J, McCall JT: Trial of penicillamine in advanced primary biliary cirrhosis. N Engl J Med 312:1011–1015, 1985

    Google Scholar 

  24. Scheuer PJ: Liver biopsy interpretation. In Biliary Disease and Cholestasis, 3rd ed. London, Bailliere Tindall, 1980, pp 36–59

    Google Scholar 

  25. Fainaru M, Deckelbaum RJ, Galbus MS: Apolipoproteins in human fetal blood and amniotic fluid in mid-trimester pregnancy. Prenat Diagn 1:125–129, 1981

    Google Scholar 

  26. Friedewald WT, Levy R, Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma without use of preparative ultracentrifuge. Clin Chem 18:499–502, 1972

    Google Scholar 

  27. Frederich RC, Lollmann B, Hamann A, Napolitano Rosen A, Kahn BB, Lowell BB, Flier JS: Expression of ob RNA and its encoded protein in rodents. Impacts of nutrition and obesity. J Clin Invest 56:1658–1663, 1995

    Google Scholar 

  28. Maffei M, Fei H, Lee GH, Dani C, Leroy P, Zhang Y, Proenca R, Negrel R, Ailhaud G, Friedman JM: Increased expression in adipocytes of ob RNA in mice with lesions of the hypothalamus and with mutations at the db locus. Proc Natl Acad Sci USA 92:6957–6960, 1995

    Google Scholar 

  29. Taylor R, Heine RJ, Collins J, James OF, Alberti KG: Insulin action in cirrhosis. Hepatology 5:64–71, 1985

    Google Scholar 

  30. Couillard C, Lamarche B, Mauriege P, Cantin B, Dagenais GR, Moorjani S, Lupien PJ, Despres JP: Leptinemia is not a risk factor for ischemic heart disease in men. Diabetes Care 21:782–786, 1998

    Google Scholar 

  31. Saladin R, De Vos P, Guerre-Millo M, Leturgue A, Girard J, Staels B, Auwerx J: Transient increase in obese gene expression after food intake or insulin administration. Nature 377:527–529, 1995

    Google Scholar 

  32. MacDougald OA, Hwang CS, Fan H, Lane MD: Regulated expression of the obese gene product (leptin) in white adipose tissue and 3T3—L1 adipocytes. Proc Natl Acad Sci USA 92:9034–9037, 1995

    Google Scholar 

  33. Richardson RA, Davidson HI, Hinds A, Cowan S, Rae P, Garden OJ: Influence of the metabolic sequelae of liver cirrhosis on nutritional intake. Am J Clin Nutr 69:331–337, 1999

    Google Scholar 

  34. McCullough AJ, Mullen KD, Kalkan SC: Measurements of total body and extracellular water in patients with and without ascites. Hepatology 14:1102–1111, 1991

    Google Scholar 

  35. Guechot J, Chazouilleres O, Loria A, Hannoun L, Balladur P, Parc R, Giboundeau J, Poupon R: Effect of liver transplantation on sex steroids in male patients with alcohol induced or post-viral hepatitis advanced liver disease. J Hepatol 20:426–430, 1994

    Google Scholar 

  36. Lin HZ, Yang SQ, Zeldin G, Diehl AM: Chronic ethanol consumption induces the production of tumor necrosis factoralpha and related cytokines in liver and adipose tissue. Alcohol Clin Exp Res 22:231S–237S, 1998

    Google Scholar 

  37. Ben-Ari Z, Baruch Y, Tur-Kaspa R, Fainaru M: Basal and post-methionine serum homocysteine and lipoprotein abnormalities in patients with primary biliary cirrhosis. Hepatology 30(no.4 part 2):475A, 1999

    Google Scholar 

  38. Lopez-Soriano J, Carbo N, Lopez-Soriano FJ, Argiles JM: Short term effects of leptin on lipid metabolism in the rat. FEBS Lett 431:371–374, 1998

    Google Scholar 

  39. Paolisso G, Ammendola S, Del-Buono A, Gambardella A, Riondino M, Tagliamonte MR, Rizzo MR, Carella C, Varricchio M: Serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in healthy centenarians: Relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function. J Clin Endocrinol Metab 82:2204–2209, 1997

    Google Scholar 

  40. Jahn CE, Schaefer EJ, Taam LA, Hoffnagle JH, Lindgren FT, Alberts JJ, Jones EA, Brewer HB: Lipoprotein abnormalities in primary biliary cirrhosis: association with hepatic lipase inhibition as well as altered cholesterol esterification. Gastroenterology 89:1266–1278, 1985

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine D, Rabin Medical Center, Petah Tiqva and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Ziv Ben-Ari, Varda Manhaim & Ran Tur-Kaspa

  2. Department of Medicine A, Rabin Medical Center, Petah Tiqva and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Zahava Schafer & Menahem Fainaru

  3. Epidemiology Unit, Rabin Medical Center, Petah Tiqva and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Jaqueline Sulkes

Authors
  1. Ziv Ben-Ari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zahava Schafer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jaqueline Sulkes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Varda Manhaim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ran Tur-Kaspa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Menahem Fainaru
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ben-Ari, Z., Schafer, Z., Sulkes, J. et al. Alterations in Serum Leptin in Chronic Liver Disease. Dig Dis Sci 47, 183–189 (2002). https://doi.org/10.1023/A:1013248427783

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1013248427783

Search

Navigation