Skip to main content
SpringerLink
Log in

Regeneration of Liver with Marked Fatty Change Following Partial Hepatectomy in Rats

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

Abstract

Resection of liver for primary and metastatic tumors and living donor liver transplantation has become a common clinical practice. The success of recovery depends on the regeneration and functions of the remnant liver. However, information on the regenerative potential of liver with steatosis and steatohepatitis, a common clinical problem in this country, is incomplete. Therefore, we evaluated regeneration after two-thirds partial hepatectomy (PH) in male F-344 rats with marked steatosis and mild steatohepatitis induced by feeding choline-deficient diet. Choline-deficient rats and control rats were killed at 24, 36, 48, 72, and 96 h after PH. Liver regeneration was determined by measuring mitotic activity and bromodeoxyuridine (BrdU) labeling in hepatocytes. Livers of rats maintained on the choline-deficient diet showed marked steatosis and mild steatohepatitis. In these animals the levels of serum and liver triacylglycerols (TG) were low and very high, respectively, when compared to controls. In control rats mitotic and BrdU labeling indices were maximal at 24 h followed by a rapid decline, whereas in choline-deficient rats both these indices increased significantly at 36 h and decreased gradually over the next 60 h. By 96 h the size of livers in both groups was comparable. The results of this study indicate that regeneration in the liver of rats with marked steatosis is not impaired.

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. Brown RS, Lake JR: Liver transplantation. Curr Hepatol 16:353–406, 1997

    Google Scholar 

  2. Fong Y, Salo J: Surgical therapy of hepatic colorectal metastasis. Semin Oncol 26:514–523, 1995

    Google Scholar 

  3. Nakagami M, Morimoto T, Itoh K, Arima Y, Yamamoto Y, Ikai I, Yamaoka Y: Patterns of restoration of remnant liver volume after graft harvesting in donors for living related liver transplantation. Transplant Proc 30: 191–199, 1998

    Google Scholar 

  4. Uemoto S, Inomata Y, Sakurai T, Egawa H, Fujita S, Kiuchi T, Hayashi M, Yasutomi M, Yamabe H, Tanaka K: Living donor liver transplantation for fulminant hepatic failure. Transplantation 70:152–157, 2000

    Google Scholar 

  5. Michalopoulos GK, DeFrances MC: Liver regeneration. Science 276:60–66, 1997

    Google Scholar 

  6. Yamanaka N, Okamoto E, Kawamura E, Kato T, Oriyama T, Fujimoto J, Furukawa K, Tanaka T, Tomoda F, Tanaka W: Dynamics of normal and injured human liver regeneration after hepatectomy as assessed on the basis of computed tomography and liver function. Hepatology 18:79–85, 1993

    Google Scholar 

  7. Bucher NLR. Liver regeneration. Then and now. In Liver regeneration and Carcinogenesis. RL Jirtle (ed). New York, Academic Press, 1995; pp 1–25

    Google Scholar 

  8. Diehl AM: Nutrition, hormones, metabolism, and liver regeneration. Semin Liver Dis 11:315–340, 1995

    Google Scholar 

  9. Sandgren EP, Luetteke NC, Palmiter RD, Brinster L, Lee DC: Overexpression of TGF-a in transgenic mice: Induction of epithelial hyperplasia, pancreatic metaplasia and carcinoma of the breast. Cell 61:1121–1135, 1990

    Google Scholar 

  10. Fausto N: Lessons from genetically engineered animal models. V. Knocking out genes to study liver regeneration: Present and future. Am J Physiol 277:G917–G921, 1999

    Google Scholar 

  11. Chou MW, Shaddock JG, Kong J, Hart RW, Casciano DA: Effect of dietary restriction on partial hepatectomy-induced liver regeneration of aged F344 rats. Cancer Lett 91:191–197, 1995

    Google Scholar 

  12. Burt AD, Mutton A, Day CP: Diagnosis and interpretation of steatosis and steatohepatitis. Semin Diag Pathol 15:246–258, 1998

    Google Scholar 

  13. Fong DG, Nehra V, Lindor KD, Buchman AL: Metabolic and nutritional considerations in nonalcoholic fatty liver. Hepatology 32:3–9, 2000

    Google Scholar 

  14. Kuczmarski RJ, Carroll MD, Flegal KM, Troiano RP: Varying body mass index cutoff points to describe overweight prevelance among US adults. NHANES 111 (1988-1994). Obes Res 5:542–548, 1997

    Google Scholar 

  15. Bellentani S, Saccocio G, Masutti, Croce LS, Brandi G, Sasso F, Cristanini G: Prevalence of and risk factors for hepatic steatosis in northern Italy. Ann Intern Med 132:112–117, 2000

    Google Scholar 

  16. Todo S, Demetris AJ, Makowka L, Teperman L, Podesta L, Shaver T, Tzakis A, Starzl TE: Primary nonfunction of hepatic allografts with preexisting fatty infiltration. Transplantation 47:903–905, 1989

    Google Scholar 

  17. Adam A, Reynes M, Johann M, Morino M, Astarcioglu I, Kafetzis I, Castaing D, Bismuth H: The outcome of steatotic grafts in liver transplantation. Transplant Proc 23:1538–1540, 1991

    Google Scholar 

  18. Teramoto K, Bowers JL, Khettry U, Palombo JD, Clouse ME: A rat fatty liver transplant model. Transplantation 55:737–741, 1993

    Google Scholar 

  19. Higgins GM, Anderson RM: Experimental pathology of the liver: Restoration of the liver in the white rat following partial removal. Arch Pathol 12:186–202, 1931

    Google Scholar 

  20. Hashimoto T, Cook WS, Qi C, Yeldandi AV, Reddy JK, Rao MS: Defect in peroxisome proliferator-activated receptor α-inducible fatty acid oxidation determines the severity of hepatic steatosis in response to fasting. J Biol Chem 275:28918–28928, 2000

    Google Scholar 

  21. Ledda-Columbano GM, Pibiri, Loi R, Perra A, Shinozuka H, Columbano A: Early increase in cyclin-D1 expression and accelerated entry of mouse hepatocytes into S phase after administration of the mitogen 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene. Am J Pathol 156:91–97, 2000

    Google Scholar 

  22. Behrns KE, Tsiotos GG, DeSouza NF, Krishna MK, Ludwig J, Nagorney M: Hepatic steatosis as a potential risk factor for major hepatic resection. J Gastrointest Surg 2:292–298, 1998

    Google Scholar 

  23. Selzner M, Clavien P: Failure of regeneration of the steatotic rat liver: Disruption at two different levels in the regeneration pathway. Hepatology 31:35–42, 2000

    Google Scholar 

  24. Zhang B, Weltman M, Farrell GC: Does steatohepatitis impair liver regeneration? A study in a dietary model of non-alcoholic steatohepatitis in rats. J Gastroenterol Hepatol 14:133–137, 1999

    Google Scholar 

  25. MacDonald RA, Rogers AE, Pechet G: Regeneration of the liver. Relation of regenerative response to size of partial hepatectomy. Lab Invest 11:544–548, 1962

    Google Scholar 

  26. Goshal AK, Ahluwalia M, Farber E: The rapid induction of liver cell death in rats fed a choline-deficient methionine-low diet. Am J Pathol 113:309–314, 1983

    Google Scholar 

  27. Ghoshal AK, Farber E: Choline deficiency, lipotrope deficiency and the development of liver disease including liver cancer: A new perspective. Lab Invest 68:255–260, 1993

    Google Scholar 

  28. Yao Z, Vance D: The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes. J Biol Chem 263:2998–3004, 1988

    Google Scholar 

  29. Day CP, James OFW: Hepatic steatosis: Innocent bystander or guilty party? Hepatology 27:1463–1465, 1998.

    Google Scholar 

  30. Bloomstrand R, Kager L, Lautto O: Studies on the ethanol induced decrease of acid oxidation in rat and human liver slices. Life Sci 13:1131–1141, 1973

    Google Scholar 

  31. Rao MS, Reddy JK: Cell and tissue adaptation. In Cellular and Molecular Pathogenesis AE Sirica (ed). New York, Lippincott-Raven, publishers. 1996, pp 57–77

  32. Sherlock S: Alcoholic liver disease. Lancet 345:227–229, 1995

    Google Scholar 

  33. Fromenty B, Pessayre D: Inhibition of mitochondrial beta oxidation as a mechanism of hepatotoxicity. Pharmacol Ther 67:101–154, 1995

    Google Scholar 

  34. Reddy JK, Mannaerts GP: Peroxisomal lipid metabolism. Annu Rev Nutr 14:343–370, 1994

    Google Scholar 

  35. Rao MS, Reddy JK: The effect of microvesicular fatty change on liver regeneration after partial hepatectomy. Hepato-Gastroenterology 47:912–915, 2000

    Google Scholar 

  36. Yang SQ, Lin HZ, Yin M, Albrecht JH, Diehl AM: Effect of chronic ethanol consumption on cytokine regulation of liver regeneration. Am J Physiol 275:G696–G704, 1998

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology and Transplantation Surgery, Northwestern University Medical School, Chicago, Illinois, 60611

    M.S. Rao, K. Papreddy, M. Abecassis & T. Hashimoto

Authors
  1. M.S. Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Papreddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Abecassis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. Hashimoto
    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

Rao, M., Papreddy, K., Abecassis, M. et al. Regeneration of Liver with Marked Fatty Change Following Partial Hepatectomy in Rats. Dig Dis Sci 46, 1821–1826 (2001). https://doi.org/10.1023/A:1010654908938

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1010654908938

Search

Navigation