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. 1985 Mar;75(3):976–986. doi: 10.1172/JCI111799

Effects of chronic ethanol intake on mobilization and excretion of cholesterol in baboons.

C Karsenty, E Baraona, M J Savolainen, C S Lieber
PMCID: PMC423641  PMID: 3980733

Abstract

To investigate the effects of chronic ethanol administration on the mobilization and excretion of cholesterol, turnover and balance studies were carried out in baboons pair-fed cholesterol-free diets containing 50% of energy either as ethanol or as additional carbohydrate for several years. Ethanol feeding increased free cholesterol in all plasma lipoprotein fractions, and esterified cholesterol in very low density lipoprotein, intermediate density lipoprotein, and high density lipoprotein (HDL). The major increase occurred in HDL, mainly as esterified cholesterol. The latter was associated with decreased transfer of esterified cholesterol from HDL to low density lipoprotein. By contrast, the smaller increase in HDL-free cholesterol was associated with increased turnover in the plasma, increased splanchnic uptake, and increased fecal excretion of plasma cholesterol, mainly as neutral steroids. Cholesterol extraction predominated over release in the splanchnic vascular bed, suggesting that the excess of cholesterol excreted in the feces originated in extrasplanchnic tissues. Thus, these findings indicate that alcohol consumption favors mobilization of tissue free cholesterol for hepatic removal and excretion. By contrast the increase in HDL-cholesterol (mainly esterified) appears to be a poor indicator of cholesterol mobilization.

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Selected References

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  1. AMENTA J. S. A RAPID CHEMICAL METHOD FOR QUANTIFICATION OF LIPIDS SEPARATED BY THIN-LAYER CHROMATOGRAPHY. J Lipid Res. 1964 Apr;5:270–272. [PubMed] [Google Scholar]
  2. Allain C. C., Poon L. S., Chan C. S., Richmond W., Fu P. C. Enzymatic determination of total serum cholesterol. Clin Chem. 1974 Apr;20(4):470–475. [PubMed] [Google Scholar]
  3. Baraona E., Lieber C. S. Efcts of chronic ethanol feeding on serum lipoprotein metabolism in the rat. J Clin Invest. 1970 Apr;49(4):769–778. doi: 10.1172/JCI106290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baraona E., Pirola R. C., Lieber C. S. Pathogenesis of postprandial hyperlipemia in rats fed ethanol-containing diets. J Clin Invest. 1973 Feb;52(2):296–303. doi: 10.1172/JCI107185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bronzert T. J., Brewer H. B., Jr New micromethod for measuring cholesterol in plasma lipoprotein fractions. Clin Chem. 1977 Nov;23(11):2089–2098. [PubMed] [Google Scholar]
  6. CAESAR J., SHALDON S., CHIANDUSSI L., GUEVARA L., SHERLOCK S. The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci. 1961 Aug;21:43–57. [PubMed] [Google Scholar]
  7. Castelli W. P., Doyle J. T., Gordon T., Hames C. G., Hjortland M. C., Hulley S. B., Kagan A., Zukel W. J. Alcohol and blood lipids. The cooperative lipoprotein phenotyping study. Lancet. 1977 Jul 23;2(8030):153–155. doi: 10.1016/s0140-6736(77)90176-3. [DOI] [PubMed] [Google Scholar]
  8. Chapman M. J. Animal lipoproteins: chemistry, structure, and comparative aspects. J Lipid Res. 1980 Sep;21(7):789–853. [PubMed] [Google Scholar]
  9. Chung B. H., Wilkinson T., Geer J. C., Segrest J. P. Preparative and quantitative isolation of plasma lipoproteins: rapid, single discontinuous density gradient ultracentrifugation in a vertical rotor. J Lipid Res. 1980 Mar;21(3):284–291. [PubMed] [Google Scholar]
  10. Cohen B. I., Raicht R. F. Sterol metabolism in the rat: effect of alcohol on sterol metabolism in two strains of rats. Alcohol Clin Exp Res. 1981 Spring;5(2):225–229. doi: 10.1111/j.1530-0277.1981.tb04893.x. [DOI] [PubMed] [Google Scholar]
  11. Crouse J. R., Grundy S. M. Effects of alcohol on plasma lipoproteins and cholesterol and triglyceride metabolism in man. J Lipid Res. 1984 May;25(5):486–496. [PubMed] [Google Scholar]
  12. DURITZ G., TRUITT E. B., Jr A RAPID METHOD FOR THE SIMULTANEOUS DETERMINATION OF ACETALDEHYDE AND ETHANOL IN BLOOD USING GAS CHROMATOGRAPHY. Q J Stud Alcohol. 1964 Sep;25:498–510. [PubMed] [Google Scholar]
  13. Davignon J., Simmonds W. J., Ahrens E. H. Usefulness of chromic oxide as an internal standard for balance studies in formula-fed patients and for assessment of colonic function. J Clin Invest. 1968 Jan;47(1):127–138. doi: 10.1172/JCI105703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Eggen D. A. Cholesterol metabolism in rhesus monkey, squirrel monkey, and baboon. J Lipid Res. 1974 Mar;15(2):139–145. [PubMed] [Google Scholar]
  15. FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
  16. Fainaru M., Havel R. J., Imaizumi K. Apoprotein content of plasma lipoproteins of the rat separated by gel chromatography or ultracentrifugation. Biochem Med. 1977 Jun;17(3):347–355. doi: 10.1016/0006-2944(77)90040-0. [DOI] [PubMed] [Google Scholar]
  17. Fielding P. E., Fielding C. J. A cholesteryl ester transfer complex in human plasma. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3327–3330. doi: 10.1073/pnas.77.6.3327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. GRUNDY S. M., AHRENS E. H., Jr, MIETTINEN T. A. QUANTITATIVE ISOLATION AND GAS--LIQUID CHROMATOGRAPHIC ANALYSIS OF TOTAL FECAL BILE ACIDS. J Lipid Res. 1965 Jul;6:397–410. [PubMed] [Google Scholar]
  19. GURPIDE E., MANN J., SANDBERG E. DETERMINATION OF KINETIC PARAMETERS INA TWO-POOL SYSTEM BY ADMINISTRATION OF ONE OR MORE TRACERS. Biochemistry. 1964 Sep;3:1250–1255. doi: 10.1021/bi00897a012. [DOI] [PubMed] [Google Scholar]
  20. Goodman D. S., Noble R. P. Turnover of plasma cholesterol in man. J Clin Invest. 1968 Feb;47(2):231–241. doi: 10.1172/JCI105719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Grundy S. M., Ahrens E. H., Jr An evaluation of the relative merits of two methods for measuring the balance of sterols in man: isotopic balance versus chromatographic analysis. J Clin Invest. 1966 Sep;45(9):1503–1515. doi: 10.1172/JCI105457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Johansson B. G., Laurell C. B. Disorders of serum alpha-lipoproteins after alcoholic intoxication. Scand J Clin Lab Invest. 1969 May;23(3):231–233. doi: 10.3109/00365516909077654. [DOI] [PubMed] [Google Scholar]
  23. Klein R. L., Rudel L. L. Cholesterol absorption and transport in thoracic duct lymph lipoproteins of nonhuman primates. Effect of dietary cholesterol level. J Lipid Res. 1983 Apr;24(4):343–356. [PubMed] [Google Scholar]
  24. Lefevre A. F., DeCarli L. M., Lieber C. S. Effect of ethanol on cholesterol and bile acid metabolism. J Lipid Res. 1972 Jan;13(1):48–55. [PubMed] [Google Scholar]
  25. Lieber C. S., Decarli L. M. Animal models of ethanol dependence and liver injury in rats and baboons. Fed Proc. 1976 Apr;35(5):1232–1236. [PubMed] [Google Scholar]
  26. MIETTINEN T. A., AHRENS E. H., Jr, GRUNDY S. M. QUANTITATIVE ISOLATION AND GAS--LIQUID CHROMATOGRAPHIC ANALYSIS OF TOTAL DIETARY AND FECAL NEUTRAL STEROIDS. J Lipid Res. 1965 Jul;6:411–424. [PubMed] [Google Scholar]
  27. Mak K. M., Lieber C. S. Alterations in endothelial fenestrations in liver sinusoids of baboons fed alcohol: a scanning electron microscopic study. Hepatology. 1984 May-Jun;4(3):386–391. doi: 10.1002/hep.1840040306. [DOI] [PubMed] [Google Scholar]
  28. Miller N. E., Nestel P. J., Clifton-Bligh P. Relationships between plasma lipoprotein cholesterol concentrations and the pool size and metabolism of cholesterol in man. Atherosclerosis. 1976 May-Jun;23(3):535–547. doi: 10.1016/0021-9150(76)90013-7. [DOI] [PubMed] [Google Scholar]
  29. Nestel P. J., Miller N. E. Cholesterol kinetics and faecal steroid excretion in subjects with primary hyperalphalipoproteinaemia. Atherosclerosis. 1980 May;36(1):127–134. doi: 10.1016/0021-9150(80)90206-3. [DOI] [PubMed] [Google Scholar]
  30. Nestel P. J., Simons L. A., Homma Y. Effects of ethanol on bile acid and cholesterol metabolism. Am J Clin Nutr. 1976 Sep;29(9):1007–1015. doi: 10.1093/ajcn/29.9.1007. [DOI] [PubMed] [Google Scholar]
  31. Noble R. P. Electrophoretic separation of plasma lipoproteins in agarose gel. J Lipid Res. 1968 Nov;9(6):693–700. [PubMed] [Google Scholar]
  32. Rothblat G. H., Phillips M. C. Mechanism of cholesterol efflux from cells. Effects of acceptor structure and concentration. J Biol Chem. 1982 May 10;257(9):4775–4782. [PubMed] [Google Scholar]
  33. Rudel L. L., Leathers C. W., Bond M. G., Bullock B. C. Dietary ethanol-induced modifications in hyperlipoproteinemia and atherosclerosis in nonhuman primates (Macaca nemestrina). Arteriosclerosis. 1981 Mar-Apr;1(2):144–155. doi: 10.1161/01.atv.1.2.144. [DOI] [PubMed] [Google Scholar]
  34. Rudel L. L., Morris M. D. Determination of cholesterol using o-phthalaldehyde. J Lipid Res. 1973 May;14(3):364–366. [PubMed] [Google Scholar]
  35. SEARCY R. L., BERGQUIST L. M. A new color reaction for the quantitation of serum cholesterol. Clin Chim Acta. 1960 Mar;5:192–199. doi: 10.1016/0009-8981(60)90035-8. [DOI] [PubMed] [Google Scholar]
  36. SNYDER F., STEPHENS N. A simplified spectrophotometric determination of ester groups in lipids. Biochim Biophys Acta. 1959 Jul;34:244–245. doi: 10.1016/0006-3002(59)90255-0. [DOI] [PubMed] [Google Scholar]
  37. Schwartz C. C., Vlahcevic Z. R., Berman M., Meadows J. G., Nisman R. M., Swell L. Central role of high density lipoprotein in plasma free cholesterol metabolism. J Clin Invest. 1982 Jul;70(1):105–116. doi: 10.1172/JCI110582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Schwartz C. C., Vlahcevic Z. R., Halloran L. G., Swell L. An in vivo evaluation in man of the transfer of esterified cholesterol between lipoproteins and into the liver and bile. Biochim Biophys Acta. 1981 Jan 26;663(1):143–162. doi: 10.1016/0005-2760(81)90201-0. [DOI] [PubMed] [Google Scholar]
  39. Sniderman A., Thomas D., Marpole D., Teng B. Low density lipoprotein. A metabolic pathway for return of cholesterol to the splanchnic bed. J Clin Invest. 1978 Apr;61(4):867–873. doi: 10.1172/JCI109012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Stein O., Vanderhoek J., Stein Y. Cholesterol content and sterol synthesis in human skin fibroblasts and rat aortic smooth muscle cells exposed to lipoprotein-depleted serum and high density apolipoprotein/phospholipid mixtures. Biochim Biophys Acta. 1976 May 27;431(2):347–358. doi: 10.1016/0005-2760(76)90155-7. [DOI] [PubMed] [Google Scholar]
  41. Stokke K. T., Norum K. R. Determination of lecithin: cholesterol acyltransfer in human blood plasma. Scand J Clin Lab Invest. 1971 Feb;27(1):21–27. doi: 10.3109/00365517109080184. [DOI] [PubMed] [Google Scholar]
  42. Strong J. P., Eggen D. A., Newman W. P., 3rd, Martinez R. D. Naturally occurring and experimental atherosclerosis in primates. Ann N Y Acad Sci. 1968 Nov 21;149(2):882–894. doi: 10.1111/j.1749-6632.1968.tb53844.x. [DOI] [PubMed] [Google Scholar]
  43. Topping D. L., Weller R. A., Nader C. J., Calvert G. D., Illman R. J. Adaptive effects of dietary ethanol in the pig: changes in plasma high-density lipoproteins and fecal steroid excretion and mutagenicity. Am J Clin Nutr. 1982 Aug;36(2):245–250. doi: 10.1093/ajcn/36.2.245. [DOI] [PubMed] [Google Scholar]
  44. WALK L. Roentgenologic determination of the liver volume. Acta radiol. 1961 Jan;55:49–56. doi: 10.3109/00016926109173816. [DOI] [PubMed] [Google Scholar]
  45. Wilson J. D. The measurement of the exchangeable pools of cholesterol in the baboon. J Clin Invest. 1970 Apr;49(4):655–665. doi: 10.1172/JCI106277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Yano K., Rhoads G. G., Kagan A. Coffee, alcohol and risk of coronary heart disease among Japanese men living in Hawaii. N Engl J Med. 1977 Aug 25;297(8):405–409. doi: 10.1056/NEJM197708252970801. [DOI] [PubMed] [Google Scholar]
  47. van't Hooft F., Havel R. J. Metabolism of chromatographically separated rat serum lipoproteins specifically labeled with 125I-apolipoprotein E. J Biol Chem. 1981 Apr 25;256(8):3963–3968. [PubMed] [Google Scholar]

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