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. 1977 Apr 15;164(1):169–177. doi: 10.1042/bj1640169

Effect of prolonged ethanol ingestion on hepatic lipogenesis and related enzyme activities

Markku J Savolainen 1, J Kalervo Hiltunen 1, Ilmo E Hassinen 1
PMCID: PMC1164771  PMID: 18142

Abstract

1. Hepatic lipogenesis in vivo and the activities of enzymes associated with fatty acid synthesis in the liver were studied in rats fed for 21 days on liquid diets containing ethanol. 2. The ethanol-fed rats developed a moderate hepatic triacylglycerol accumulation during this period. When carbohydrate was replaced by ethanol in the diet, the rate of fatty acid synthesis was slower in the ethanol-fed rats on low-, medium- and high-fat diets than in the appropriate controls. However, when the fat/carbohydrate ratio was kept the same in the ethanol-fed and control rats, ethanol had no influence on the rate of fatty acid synthesis. 3. Glucose 6-phosphate dehydrogenase activity was lower in the ethanol-fed group. `Malic' enzyme activity did not change during the ethanol treatment when the fat/carbohydrate ratio was kept unchanged. 4. The ATP citrate lyase activity was lower in the ethanol-fed rats on all diets, whereas acetyl-CoA synthetase activity was independent of the composition of the control diet, but was lower in the ethanol-fed rats, in which the concentration of the active form of pyruvate dehydrogenase was also lower. 5. It is concluded that hepatic fatty acid synthesis does not play any major role in ethanol-induced triacylglycerol accumulation. Careful design of the diets is necessary to reveal the specific effects of ethanol on the enzymes associated with lipogenesis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Batenburg J. J., Olson M. S. Regulation of pyruvate dehydrogenase by fatty acid in isolated rat liver mitochondria. J Biol Chem. 1976 Mar 10;251(5):1364–1370. [PubMed] [Google Scholar]
  2. Burger H. G., Lee V. W., Rennie G. C. A generalized computer program for the treatment of data from competitive protein-binding assays including radioimmunoassays. J Lab Clin Med. 1972 Aug;80(2):302–312. [PubMed] [Google Scholar]
  3. CARLSON L. A. DETERMINATION OF SERUM TRIGLYCERIDES. J Atheroscler Res. 1963 Jul-Aug;3:334–336. doi: 10.1016/s0368-1319(63)80012-5. [DOI] [PubMed] [Google Scholar]
  4. Carlson C. A., Kim K. H. Regulation of hepatic acetyl coenzyme A carboxylase by phosphorylation and dephosphorylation. J Biol Chem. 1973 Jan 10;248(1):378–380. [PubMed] [Google Scholar]
  5. Coore H. G., Denton R. M., Martin B. R., Randle P. J. Regulation of adipose tissue pyruvate dehydrogenase by insulin and other hormones. Biochem J. 1971 Nov;125(1):115–127. doi: 10.1042/bj1250115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Denton R. M., Randle P. J., Martin B. R. Stimulation by calcium ions of pyruvate dehydrogenase phosphate phosphatase. Biochem J. 1972 Jun;128(1):161–163. doi: 10.1042/bj1280161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. FORSANDER O., RAIHA N., SUOMALAINEN H. Alkoholoxydation und Bildung von Acetoacetat in normaler und glykogenarmer intakter Rattenleber. Hoppe Seylers Z Physiol Chem. 1958;312(4-6):243–248. [PubMed] [Google Scholar]
  8. GORDON R. S., Jr Unesterified fatty acid in human blood plasma. II. The transport function of unesterified fatty acid. J Clin Invest. 1957 Jun;36(6 Pt 1):810–815. doi: 10.1172/JCI103486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gaertner E. B., Carroll C. Metabolic responses of white rats to balanced and imbalanced protein fed with different carbohydrates in 15 percent and 5 percent fat diets. J Nutr. 1967 Jan;91(1):69–78. doi: 10.1093/jn/91.1.69. [DOI] [PubMed] [Google Scholar]
  10. Gilman A. G. A protein binding assay for adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1970 Sep;67(1):305–312. doi: 10.1073/pnas.67.1.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Guynn R. W., Veloso D., Harris R. L., Lawson J. W., Veech R. L. Ethanol administration and the relationship of malonyl-coenzyme A concentrations to the rate of fatty acid synthesis in rat liver. Biochem J. 1973 Nov;136(3):639–647. doi: 10.1042/bj1360639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. HILL R., LINAZASORO J. M., CHEVALLIER F., CHAIKOFF I. L. Regulation of hepatic lipogenesis: the influence of dietary fats. J Biol Chem. 1958 Aug;233(2):305–310. [PubMed] [Google Scholar]
  13. HJELM M., DE VERDIERCH C. H. A METHODOLOGICAL STUDY OF THE ENZYMATIC DETERMINATION OF GLUCOSE IN BLOOD. Scand J Clin Lab Invest. 1963;15:415–428. doi: 10.3109/00365516309079764. [DOI] [PubMed] [Google Scholar]
  14. Hanson R. W., Ballard F. J. The relative significance of acetate and glucose as precursors for lipid synthesis in liver and adipose tissue from ruminants. Biochem J. 1967 Nov;105(2):529–536. doi: 10.1042/bj1050529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hiltunen J. K., Hassinen I. E. Energy-linked regulation of glucose and pyruvate oxidation in isolated perfused rat heart. Role of pyruvate dehydrogenase. Biochim Biophys Acta. 1976 Aug 13;440(2):377–390. doi: 10.1016/0005-2728(76)90072-4. [DOI] [PubMed] [Google Scholar]
  16. Hucho F., Randall D. D., Roche T. E., Burgett M. W., Pelley J. W., Reed L. J. -Keto acid dehydrogenase complexes. XVII. Kinetic and regulatory properties of pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase from bovine kidney and heart. Arch Biochem Biophys. 1972 Jul;151(1):328–340. doi: 10.1016/0003-9861(72)90504-8. [DOI] [PubMed] [Google Scholar]
  17. Johnson O., Hernell O., Olivecrona T. Effect of ethanol on utilization of plasma free fatty acids for liver triacylglycerol synthesis and its relation to hepatic triacylglycerol accumulation in rats. Lipids. 1975 Dec;10(12):765–769. doi: 10.1007/BF02532318. [DOI] [PubMed] [Google Scholar]
  18. Jungas R. L. Fatty acid synthesis in adipose tissue incubated in tritiated water. Biochemistry. 1968 Oct;7(10):3708–3717. doi: 10.1021/bi00850a050. [DOI] [PubMed] [Google Scholar]
  19. LIEBER C. S., JONES D. P., DECARLI L. M. EFFECTS OF PROLONGED ETHANOL INTAKE: PRODUCTION OF FATTY LIVER DESPITE ADEQUATE DIETS. J Clin Invest. 1965 Jun;44:1009–1021. doi: 10.1172/JCI105200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. LIEBER C. S., SCHMID R. The effect of ethanol on fatty acid metabolism; stimulation of hepatic fatty acid synthesis in vitro. J Clin Invest. 1961 Feb;40:394–399. doi: 10.1172/JCI104266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lieber C. S. Chronic alcoholic hepatic injury in experimental animals and man: biochemical pathways and nutritional factors. Fed Proc. 1967 Sep;26(5):1443–1448. [PubMed] [Google Scholar]
  22. Lieber C. S., DeCarli L. M. Quantitative relationship between amount of dietary fat and severity of alcoholic fatty liver. Am J Clin Nutr. 1970 Apr;23(4):474–478. doi: 10.1093/ajcn/23.4.474. [DOI] [PubMed] [Google Scholar]
  23. Lieber C. S. Effects of ethanol upon lipid metabolism. Lipids. 1974 Feb;9(2):103–116. doi: 10.1007/BF02532134. [DOI] [PubMed] [Google Scholar]
  24. Lieber C. S., Spritz N., DeCarli L. M. Role of dietary, adipose, and endogenously synthesized fatty acids in the pathogenesis of the alcoholic fatty liver. J Clin Invest. 1966 Jan;45(1):51–62. doi: 10.1172/JCI105323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lieber C. S., Spritz N. Effects of prolonged ethanol intake in man: role of dietary adipose, and endogenously synthesized fatty acids in the pathogenesis of the alcoholic fatty liver. J Clin Invest. 1966 Sep;45(9):1400–1411. doi: 10.1172/JCI105448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lowenstein J. M., Brunengraber H., Wadke M. Measurement of rates of lipogenesis with deuterated and tritiated water. Methods Enzymol. 1975;35:279–287. doi: 10.1016/0076-6879(75)35165-3. [DOI] [PubMed] [Google Scholar]
  27. Lowenstein J. M. Effect of (-)-hydroxycitrate on fatty acid synthesis by rat liver in vivo. J Biol Chem. 1971 Feb 10;246(3):629–632. [PubMed] [Google Scholar]
  28. MATTHES K. J., ABRAHAM S., CHAIKOFF I. L. Fatty acid synthesis from acetate by normal and diabetic rat liver homogenate fractions. II. Effect of microsomes and oxidation of substrates. J Biol Chem. 1960 Sep;235:2560–2568. [PubMed] [Google Scholar]
  29. Mayes P. A., Topping D. L. Regulation of hepatic lipogenesis by plasma free fatty acids: simultaneous studies on lipoprotein secretion, cholesterol synthesis, ketogenesis and gluconeogenesis. Biochem J. 1974 Apr;140(1):111–114. doi: 10.1042/bj1400111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. NOVAK M. COLORIMETRIC ULTRAMICRO METHOD FOR THE DETERMINATION OF FREE FATTY ACIDS. J Lipid Res. 1965 Jul;6:431–433. [PubMed] [Google Scholar]
  31. Raskin P., McGarry J. D., Foster D. W. Independence of cholesterol and fatty acid biosynthesis from cyclic adenosine monophosphate concentration in the perfused rat liver. J Biol Chem. 1974 Oct 10;249(19):6029–6032. [PubMed] [Google Scholar]
  32. Romsos D. R., Leveille G. A. Effect of dietary fructose on in vitro and in vivo fatty acid synthesis in the rat. Biochim Biophys Acta. 1974 Jul 26;360(1):1–11. doi: 10.1016/0005-2760(74)90175-1. [DOI] [PubMed] [Google Scholar]
  33. Rudack D., Chisholm E. M., Holten D. Rat liver glucose 6-phosphate dehydrogenase. Regulation by carbohydrate diet and insulin. J Biol Chem. 1971 Mar 10;246(5):1249–1254. [PubMed] [Google Scholar]
  34. STACEY R. E., LATIMER S. B., TOVE S. B. DETERMINATION OF ACYL-COA SYNTHETASE ACTIVITY FOR VOLATILE FATTY ACIDS. Biochim Biophys Acta. 1964 Apr 20;84:192–195. doi: 10.1016/0926-6542(64)90077-0. [DOI] [PubMed] [Google Scholar]
  35. SZARKOWSKA L., KLINGENBERG M. ON THE ROLE OF UBIQUINONE IN MITOCHONDRIA. SPECTROPHOTOMETRIC AND CHEMICAL MEASUREMENTS OF ITS REDOX REACTIONS. Biochem Z. 1963;338:674–697. [PubMed] [Google Scholar]
  36. Sabine J. R., Abraham S., Morris H. P. Defective dietary control of fatty acid metabolism in four transplantable rat hepatomas: numbers 5123C, 7793, 7795, and 7800. Cancer Res. 1968 Jan;28(1):46–51. [PubMed] [Google Scholar]
  37. Salmon D. M., Bowen N. L., Hems D. A. Synthesis of fatty acids in the perused mouse liver. Biochem J. 1974 Sep;142(3):611–618. doi: 10.1042/bj1420611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Siess E. A., Wieland O. H. Purification and characterization of pyruvate-dehydrogenase phosphatase from pig-heart muscle. Eur J Biochem. 1972 Mar 15;26(1):96–105. doi: 10.1111/j.1432-1033.1972.tb01744.x. [DOI] [PubMed] [Google Scholar]
  39. Thorpe M. E., Shorey C. D. Long-term alcohol administration. Its effects on the ultrastructure and lipid content of the rat liver cell. Am J Pathol. 1966 Apr;48(4):557–577. [PMC free article] [PubMed] [Google Scholar]
  40. Van Handel E. Estimation of glycogen in small amounts of tissue. Anal Biochem. 1965 May;11(2):256–265. doi: 10.1016/0003-2697(65)90013-8. [DOI] [PubMed] [Google Scholar]
  41. Volpe J. J., Lyles T. O., Roncari D. A., Vagelos P. R. Fatty acid synthetase of developing brain and liver. Content, synthesis, and degradation during development. J Biol Chem. 1973 Apr 10;248(7):2502–2513. [PubMed] [Google Scholar]
  42. Volpe J. J., Vagelos P. R. Saturated fatty acid biosynthesis and its regulation. Annu Rev Biochem. 1973;42:21–60. doi: 10.1146/annurev.bi.42.070173.000321. [DOI] [PubMed] [Google Scholar]
  43. WOLLENBERGER A., RISTAU O., SCHOFFA G. [A simple technic for extremely rapid freezing of large pieces of tissue]. Pflugers Arch Gesamte Physiol Menschen Tiere. 1960;270:399–412. [PubMed] [Google Scholar]
  44. Windmueller H. G., Spaeth A. E. Perfusion in situ with tritium oxide to measure hepatic lipogenesis and lipid secretion. Normal and orotic acid-fed rats. J Biol Chem. 1966 Jun 25;241(12):2891–2899. [PubMed] [Google Scholar]

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