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. 1974 Feb;53(2):423–430. doi: 10.1172/JCI107576

Studies of the hepatic excretory defects in essential fatty acid deficiency. Their possible relationship to the genesis of cholesterol gallstones.

I J Sarfeh 1, D A Beeler 1, D H Treble 1, J A Balint 1
PMCID: PMC301485  PMID: 11344556

Abstract

Male hamsters were fed normal and essential fatty acid (EFA)-deficient diets for at least 12 wk before bile duct cannulation. With [32P]phosphate, hepatic synthesis of lecithin was similar, but biliary excretion of newly synthesized lecithin was significantly reduced in EFA-deficient compared to that in normal hamsters. Hepatic uptake of intravenously infused taurocholate (TC) and taurochenodeoxycholate (TCDC) were similar in both groups of animals. However, biliary excretion of intravenously infused TC was significantly reduced in EFA-deficient hamsters, whereas that of TCDC-was unchanged. The absolute rate of biliary cholesterol excretion was similar in both groups. Canalicular bile flow, as measured by [14C]erythritol clearance after functional nephrectomy, was significantly lower, with both the bile salt-dependent and independent fractions of this flow being diminished in EFA-deficient hamsters infused with TC. It is concluded that EFA deficiency leads to impaired biliary excretion of taurocholate, lecithin, and water, while cholesterol transport is unaffected, and thus results in supersaturation of bile with respect to cholesterol and production of lithogenic bile.

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Selected References

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

  1. Admirand W. H., Small D. M. The physicochemical basis of cholesterol gallstone formation in man. J Clin Invest. 1968 May;47(5):1043–1052. doi: 10.1172/JCI105794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BALINT J. A., NYHAN W. L., LIETMAN P., TURNER D. A. Lipid patterns in Niemann-Pick disease. J Lab Clin Med. 1961 Oct;58:548–558. [PubMed] [Google Scholar]
  3. Balint J. A., Beeler D. A., Kyriakides E. C., Treble D. H. The effect of bile salts upon lecithin synthesis. J Lab Clin Med. 1971 Jan;77(1):122–133. [PubMed] [Google Scholar]
  4. Beeler D. A., Treble D. H., Kyriakides E. C., Balint J. A. The pathways of lecithin biosynthesis in essential fatty acid deficiency in hamsters. Biochim Biophys Acta. 1970 Oct 6;218(1):112–123. doi: 10.1016/0005-2760(70)90098-6. [DOI] [PubMed] [Google Scholar]
  5. Boyer J. L. Canalicular bile formation in the isolated perfused rat liver. Am J Physiol. 1971 Oct;221(4):1156–1163. doi: 10.1152/ajplegacy.1971.221.4.1156. [DOI] [PubMed] [Google Scholar]
  6. COLLINS F. D. Phospholipid metabolism in essential fatty acid deficient rats. Biochem Biophys Res Commun. 1962 Oct 31;9:289–292. doi: 10.1016/0006-291x(62)90041-4. [DOI] [PubMed] [Google Scholar]
  7. Dam H. Nutritional aspects of gallstone formation with particular reference to alimentary production of gallstones in laboratory animals. World Rev Nutr Diet. 1969;11:199–239. doi: 10.1159/000387579. [DOI] [PubMed] [Google Scholar]
  8. ENEROTH P. THIN-LAYER CHROMATOGRAPHY OF BILE ACIDS. J Lipid Res. 1963 Jan;4:11–16. [PubMed] [Google Scholar]
  9. Erlinger S., Dhumeaux D., Berthelot P., Dumont M. Effect of inhibitors of sodium transport on bile formation in the rabbit. Am J Physiol. 1970 Aug;219(2):416–422. doi: 10.1152/ajplegacy.1970.219.2.416. [DOI] [PubMed] [Google Scholar]
  10. Forker E. L. Bile formation in guinea pigs: analysis with inert solutes of graded molecular radius. Am J Physiol. 1968 Jul;215(1):56–62. doi: 10.1152/ajplegacy.1968.215.1.56. [DOI] [PubMed] [Google Scholar]
  11. Fukazawa T., Privett O. S., Takahaski Y. Effect of essential fatty acid deficiency on release of triglycerides by the perfused rat liver. J Lipid Res. 1970 Nov;11(6):522–527. [PubMed] [Google Scholar]
  12. GORDON B. A., KUKSIS A., BEVERIDGE J. M. Separation of bile acid conjugates by ion exchange chromatography. Can J Biochem Physiol. 1963 Jan;41:77–89. [PubMed] [Google Scholar]
  13. Gregg J. A. New solvent systems for thin-layer chromatography of bile acids. J Lipid Res. 1966 Jul;7(4):579–581. [PubMed] [Google Scholar]
  14. Hardison W. G., Apter J. T. Micellar theory of biliary cholesterol excretion. Am J Physiol. 1972 Jan;222(1):61–67. doi: 10.1152/ajplegacy.1972.222.1.61. [DOI] [PubMed] [Google Scholar]
  15. Heath T., Caple I. W., Redding P. M. Effect of the enterohepatic circulation of bile salts on the flow of bile and its content of bile salts and lipids in sheep. Q J Exp Physiol Cogn Med Sci. 1970 Apr;55(2):93–103. doi: 10.1113/expphysiol.1970.sp002067. [DOI] [PubMed] [Google Scholar]
  16. Imami R. H., Reiser S., Christiansen P. A. Effects of vitamin E and essential fatty acid deficiencies on the intestinal transport of L-valine and alpha-methyl-D-glucoside in the rat. J Nutr. 1970 Jan;100(1):101–109. doi: 10.1093/jn/100.1.101. [DOI] [PubMed] [Google Scholar]
  17. Kimelberg H. K., Papahadjopoulos D. Phospholipid requirements for (Na + + K + )-ATPase activity: head-group specificity and fatty acid fluidity. Biochim Biophys Acta. 1972 Sep 1;282(1):277–292. doi: 10.1016/0005-2736(72)90334-3. [DOI] [PubMed] [Google Scholar]
  18. Kyriakides E. C., Balint J. A. Quantitative recovery of lecithins after argentation chromatography on thin layers. J Lipid Res. 1968 Jan;9(1):142–143. [PubMed] [Google Scholar]
  19. MOSBACH E. H., KALINSKY H. J., HALPERN E., KENDALL F. E. Determination of deoxycholic and cholic acids in bile. Arch Biochem Biophys. 1954 Aug;51(2):402–410. doi: 10.1016/0003-9861(54)90495-6. [DOI] [PubMed] [Google Scholar]
  20. Metzger A. L., Adler R., Heymsfield S., Grundy S. M. Diurnal variation in biliary lipid composition. Possible role in cholesterol gallstone formation. N Engl J Med. 1973 Feb 15;288(7):333–336. doi: 10.1056/NEJM197302152880702. [DOI] [PubMed] [Google Scholar]
  21. Neiderhiser D. H., Roth H. P. Cholesterol solubilization by solutions of bile salts and bile salts plus lecithin. Proc Soc Exp Biol Med. 1968 May;128(1):221–225. doi: 10.3181/00379727-128-32983. [DOI] [PubMed] [Google Scholar]
  22. Robins S. J., Fasulo J. Mechanism of lithogenic bile production: studies in the hamster fed an essential fatty acid-deficient diet. Gastroenterology. 1973 Jul;65(1):104–114. [PubMed] [Google Scholar]
  23. Sinclair A. J., Collins F. D. Fatty livers in rats deficient in essential fatty acids. Biochim Biophys Acta. 1968 May 1;152(3):498–510. doi: 10.1016/0005-2760(68)90090-8. [DOI] [PubMed] [Google Scholar]
  24. Small D. M. Gallstones. N Engl J Med. 1968 Sep 12;279(11):588–593. doi: 10.1056/NEJM196809122791106. [DOI] [PubMed] [Google Scholar]
  25. Small D. M., Rapo S. Source of abnormal bile in patients with cholesterol gallstones. N Engl J Med. 1970 Jul 9;283(2):53–57. doi: 10.1056/NEJM197007092830201. [DOI] [PubMed] [Google Scholar]
  26. Swell L., Bell C. C., Jr, Entenman C. Bile acids and lipid metabolism. 3. Influence of bile acids on phospholipids in liver and bile of the isolated perfused dog liver. Biochim Biophys Acta. 1968 Oct 22;164(2):278–284. [PubMed] [Google Scholar]
  27. Swell L., Entenman C., Leong G. F., Holloway R. J. Bile acids and lipid metabolism. IV. Influence of bile acids on biliary and liver organelle phospholipids and cholesterol. Am J Physiol. 1968 Dec;215(6):1390–1396. doi: 10.1152/ajplegacy.1968.215.6.1390. [DOI] [PubMed] [Google Scholar]
  28. Taniguchi K., Tonomura Y. Inactivation of Na plus-K plus-dependent ATPase by phospholipase-treatment and its reactivation by phospholipids. J Biochem. 1971 Mar;69(3):543–557. [PubMed] [Google Scholar]
  29. Thistle J. L., Schoenfield L. J. Lithogenic bile among young Indian women. N Engl J Med. 1971 Jan 28;284(4):177–181. doi: 10.1056/NEJM197101282840404. [DOI] [PubMed] [Google Scholar]
  30. Wheeler H. O. Biliary excretion of bile acids, lecithin, and cholesterol in hamsters with gallstones. Gastroenterology. 1973 Jul;65(1):92–103. [PubMed] [Google Scholar]
  31. Wheeler H. O., King K. K. Biliary excretion of lecithin and cholesterol in the dog. J Clin Invest. 1972 Jun;51(6):1337–1350. doi: 10.1172/JCI106930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wheeler H. O., Ross E. D., Bradley S. E. Canalicular bile production in dogs. Am J Physiol. 1968 Apr;214(4):866–874. doi: 10.1152/ajplegacy.1968.214.4.866. [DOI] [PubMed] [Google Scholar]
  33. ZAK B. Simple rapid microtechnic for serum total cholesterol. Am J Clin Pathol. 1957 May;27(5):583–588. doi: 10.1093/ajcp/27.5_ts.583. [DOI] [PubMed] [Google Scholar]

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