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. 2001 Jul 15;357(Pt 2):481–487. doi: 10.1042/0264-6021:3570481

Comparison of the effects of dietary n-3 and n-6 polyunsaturated fatty acids on very-low-density lipoprotein secretion when delivered to hepatocytes in chylomicron remnants.

X Zheng 1, M Avella 1, K M Botham 1
PMCID: PMC1221975  PMID: 11439098

Abstract

The effects of chylomicron remnants enriched in n-3 or n-6 polyunsaturated fatty acids (derived from fish or corn oil respectively) on the secretion of very-low-density lipoprotein (VLDL) lipid and apolipoprotein B (apoB) by rat hepatocytes in culture was investigated. Remnants were prepared in vivo from chylomicrons obtained from rats given an oral dose of fish or corn oil and incubated with cultured hepatocytes for up to 16 h. The medium was then removed and the secretion of cholesterol and triacylglycerol into the whole medium or the rho<1.050 g/ml fraction during the following 7-24 h was determined. After exposure of the cells to fish-oil as compared with corn-oil remnants, secretion of both cholesterol and triacylglycerol into the whole medium was decreased by 25-35%, and secretion into the rho<1.050 g/ml fraction was decreased by 20-25%. In addition, the levels of apoB48 found in the rho<1.050 g/ml fraction were significantly lower in cells treated with fish-oil rather than corn-oil remnants, although the levels of apoB100 remained unchanged. The expression of mRNA for apoB, as determined by reverse-transcriptase PCR, however, was not significantly changed after exposure of the cells to both types of remnants. These results demonstrate that the effects of dietary n-3 polyunsaturated fatty acids in depressing hepatic VLDL secretion occur directly when they are delivered to the liver from the intestine in chylomicron remnants, and that the secretion, but not the synthesis, of apoB is targeted.

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Selected References

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  1. AHRENS E. H., Jr Seminar on atherosclerosis: nutritional factors and serum lipid levels. Am J Med. 1957 Dec;23(6):928–952. doi: 10.1016/0002-9343(57)90303-0. [DOI] [PubMed] [Google Scholar]
  2. Benner K. G., Sasaki A., Gowen D. R., Weaver A., Connor W. E. The differential effect of eicosapentaenoic acid and oleic acid on lipid synthesis and VLDL secretion in rabbit hepatocytes. Lipids. 1990 Sep;25(9):534–540. doi: 10.1007/BF02537160. [DOI] [PubMed] [Google Scholar]
  3. Bravo E., Ortu G., Cantafora A., Lambert M. S., Avella M., Mayes P. A., Botham K. M. Comparison of the hepatic uptake and processing of cholesterol from chylomicrons of different fatty acid composition in the rat in vivo. Biochim Biophys Acta. 1995 Oct 5;1258(3):328–336. doi: 10.1016/0005-2760(95)00141-x. [DOI] [PubMed] [Google Scholar]
  4. Brewer H. B., Jr Hypertriglyceridemia: changes in the plasma lipoproteins associated with an increased risk of cardiovascular disease. Am J Cardiol. 1999 May 13;83(9B):3F–12F. doi: 10.1016/s0002-9149(99)00308-2. [DOI] [PubMed] [Google Scholar]
  5. Brown A. M., Baker P. W., Gibbons G. F. Changes in fatty acid metabolism in rat hepatocytes in response to dietary n-3 fatty acids are associated with changes in the intracellular metabolism and secretion of apolipoprotein B-48. J Lipid Res. 1997 Mar;38(3):469–481. [PubMed] [Google Scholar]
  6. Brown A. M., Castle J., Hebbachi A. M., Gibbons G. F. Administration of n-3 fatty acids in the diets of rats or directly to hepatocyte cultures results in different effects on hepatocellular ApoB metabolism and secretion. Arterioscler Thromb Vasc Biol. 1999 Jan;19(1):106–114. doi: 10.1161/01.atv.19.1.106. [DOI] [PubMed] [Google Scholar]
  7. Castelli W. P., Garrison R. J., Wilson P. W., Abbott R. D., Kalousdian S., Kannel W. B. Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA. 1986 Nov 28;256(20):2835–2838. [PubMed] [Google Scholar]
  8. Connor W. E. The beneficial effects of omega-3 fatty acids: cardiovascular disease and neurodevelopment. Curr Opin Lipidol. 1997 Feb;8(1):1–3. doi: 10.1097/00041433-199702000-00001. [DOI] [PubMed] [Google Scholar]
  9. Ford R. P., Botham K. M., Suckling K. E., Boyd G. S. Characterisation of rat hepatocyte monolayers for investigation of the metabolism of bile salts. Biochim Biophys Acta. 1985 Sep 11;836(2):185–191. doi: 10.1016/0005-2760(85)90065-7. [DOI] [PubMed] [Google Scholar]
  10. Geelen M. J., Schoots W. J., Bijleveld C., Beynen A. C. Dietary medium-chain fatty acids raise and (n-3) polyunsaturated fatty acids lower hepatic triacylglycerol synthesis in rats. J Nutr. 1995 Oct;125(10):2449–2456. doi: 10.1093/jn/125.10.2449. [DOI] [PubMed] [Google Scholar]
  11. Harris W. S., Connor W. E., Illingworth D. R., Rothrock D. W., Foster D. M. Effects of fish oil on VLDL triglyceride kinetics in humans. J Lipid Res. 1990 Sep;31(9):1549–1558. [PubMed] [Google Scholar]
  12. Harris W. S. Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review. J Lipid Res. 1989 Jun;30(6):785–807. [PubMed] [Google Scholar]
  13. Hegsted D. M., McGandy R. B., Myers M. L., Stare F. J. Quantitative effects of dietary fat on serum cholesterol in man. Am J Clin Nutr. 1965 Nov;17(5):281–295. doi: 10.1093/ajcn/17.5.281. [DOI] [PubMed] [Google Scholar]
  14. Homan R., Grossman J. E., Pownall H. J. Differential effects of eicosapentaenoic acid and oleic acid on lipid synthesis and secretion by HepG2 cells. J Lipid Res. 1991 Feb;32(2):231–241. [PubMed] [Google Scholar]
  15. Isusi E., Aspichueta P., Liza M., Hernández M. L., Díaz C., Hernández G., Martínez M. J., Ochoa B. Short- and long-term effects of atorvastatin, lovastatin and simvastatin on the cellular metabolism of cholesteryl esters and VLDL secretion in rat hepatocytes. Atherosclerosis. 2000 Dec;153(2):283–294. doi: 10.1016/s0021-9150(00)00407-x. [DOI] [PubMed] [Google Scholar]
  16. Joyce C., Skinner K., Anderson R. A., Rudel L. L. Acyl-coenzyme A:cholesteryl acyltransferase 2. Curr Opin Lipidol. 1999 Apr;10(2):89–95. doi: 10.1097/00041433-199904000-00002. [DOI] [PubMed] [Google Scholar]
  17. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  18. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  19. Lambert M. S., Botham K. M., Mayes P. A. Modification of the fatty acid composition of dietary oils and fats on incorporation into chylomicrons and chylomicron remnants. Br J Nutr. 1996 Sep;76(3):435–445. doi: 10.1079/bjn19960048. [DOI] [PubMed] [Google Scholar]
  20. Lambert M. S., Botham K. M., Mayes P. A. Variations in composition of dietary fats affect hepatic uptake and metabolism of chylomicron remnants. Biochem J. 1995 Sep 15;310(Pt 3):845–852. doi: 10.1042/bj3100845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lang C. A., Davis R. A. Fish oil fatty acids impair VLDL assembly and/or secretion by cultured rat hepatocytes. J Lipid Res. 1990 Nov;31(11):2079–2086. [PubMed] [Google Scholar]
  22. Lau P. P., Xiong W. J., Zhu H. J., Chen S. H., Chan L. Apolipoprotein B mRNA editing is an intranuclear event that occurs posttranscriptionally coincident with splicing and polyadenylation. J Biol Chem. 1991 Oct 25;266(30):20550–20554. [PubMed] [Google Scholar]
  23. Lin Y., Smit M. J., Havinga R., Verkade H. J., Vonk R. J., Kuipers F. Differential effects of eicosapentaenoic acid on glycerolipid and apolipoprotein B metabolism in primary human hepatocytes compared to HepG2 cells and primary rat hepatocytes. Biochim Biophys Acta. 1995 Apr 28;1256(1):88–96. doi: 10.1016/0005-2760(95)00006-x. [DOI] [PubMed] [Google Scholar]
  24. Martin M. J., Hulley S. B., Browner W. S., Kuller L. H., Wentworth D. Serum cholesterol, blood pressure, and mortality: implications from a cohort of 361,662 men. Lancet. 1986 Oct 25;2(8513):933–936. doi: 10.1016/s0140-6736(86)90597-0. [DOI] [PubMed] [Google Scholar]
  25. Miller M. Current perspectives on the management of hypertriglyceridemia. Am Heart J. 2000 Aug;140(2):232–240. doi: 10.1067/mhj.2000.108001. [DOI] [PubMed] [Google Scholar]
  26. Mindham M. A., Mayes P. A. A simple and rapid method for the preparation of apolipoproteins for electrophoresis. J Lipid Res. 1992 Jul;33(7):1084–1088. [PubMed] [Google Scholar]
  27. Nossen J. O., Rustan A. C., Gloppestad S. H., Målbakken S., Drevon C. A. Eicosapentaenoic acid inhibits synthesis and secretion of triacylglycerols by cultured rat hepatocytes. Biochim Biophys Acta. 1986 Oct 24;879(1):56–65. doi: 10.1016/0005-2760(86)90266-3. [DOI] [PubMed] [Google Scholar]
  28. Olivecrona G., Olivecrona T. Triglyceride lipases and atherosclerosis. Curr Opin Lipidol. 1995 Oct;6(5):291–305. doi: 10.1097/00041433-199510000-00009. [DOI] [PubMed] [Google Scholar]
  29. Olofsson S. O., Asp L., Borén J. The assembly and secretion of apolipoprotein B-containing lipoproteins. Curr Opin Lipidol. 1999 Aug;10(4):341–346. doi: 10.1097/00041433-199908000-00008. [DOI] [PubMed] [Google Scholar]
  30. Parks J. S., Johnson F. L., Wilson M. D., Rudel L. L. Effect of fish oil diet on hepatic lipid metabolism in nonhuman primates: lowering of secretion of hepatic triglyceride but not apoB. J Lipid Res. 1990 Mar;31(3):455–466. [PubMed] [Google Scholar]
  31. Parks J. S., Wilson M. D., Johnson F. L., Rudel L. L. Fish oil decreases hepatic cholesteryl ester secretion but not apoB secretion in African green monkeys. J Lipid Res. 1989 Oct;30(10):1535–1544. [PubMed] [Google Scholar]
  32. Phillipson B. E., Rothrock D. W., Connor W. E., Harris W. S., Illingworth D. R. Reduction of plasma lipids, lipoproteins, and apoproteins by dietary fish oils in patients with hypertriglyceridemia. N Engl J Med. 1985 May 9;312(19):1210–1216. doi: 10.1056/NEJM198505093121902. [DOI] [PubMed] [Google Scholar]
  33. Redgrave T. G. Formation and metabolism of chylomicrons. Int Rev Physiol. 1983;28:103–130. [PubMed] [Google Scholar]
  34. Ribeiro A., Mangeney M., Cardot P., Loriette C., Rayssiguier Y., Chambaz J., Bereziat G. Effect of dietary fish oil and corn oil on lipid metabolism and apolipoprotein gene expression by rat liver. Eur J Biochem. 1991 Mar 14;196(2):499–507. doi: 10.1111/j.1432-1033.1991.tb15842.x. [DOI] [PubMed] [Google Scholar]
  35. Rustan A. C., Drevon C. A. Eicosapentaenoic acid inhibits hepatic production of very low density lipoprotein. J Intern Med Suppl. 1989;731:31–38. doi: 10.1111/j.1365-2796.1989.tb01433.x. [DOI] [PubMed] [Google Scholar]
  36. Rustan A. C., Nossen J. O., Christiansen E. N., Drevon C. A. Eicosapentaenoic acid reduces hepatic synthesis and secretion of triacylglycerol by decreasing the activity of acyl-coenzyme A:1,2-diacylglycerol acyltransferase. J Lipid Res. 1988 Nov;29(11):1417–1426. [PubMed] [Google Scholar]
  37. Rustan A. C., Nossen J. O., Osmundsen H., Drevon C. A. Eicosapentaenoic acid inhibits cholesterol esterification in cultured parenchymal cells and isolated microsomes from rat liver. J Biol Chem. 1988 Jun 15;263(17):8126–8132. [PubMed] [Google Scholar]
  38. Scott J. The molecular and cell biology of apolipoprotein-B. Mol Biol Med. 1989 Feb;6(1):65–80. [PubMed] [Google Scholar]
  39. Shelness G. S., Ingram M. F., Huang X. F., DeLozier J. A. Apolipoprotein B in the rough endoplasmic reticulum: translation, translocation and the initiation of lipoprotein assembly. J Nutr. 1999 Feb;129(2S):456S–462S. doi: 10.1093/jn/129.2.456S. [DOI] [PubMed] [Google Scholar]
  40. Shepherd J., Packard C. J., Grundy S. M., Yeshurun D., Gotto A. M., Jr, Taunton O. D. Effects of saturated and polyunsaturated fat diets on the chemical composition and metabolism of low density lipoproteins in man. J Lipid Res. 1980 Jan;21(1):91–99. [PubMed] [Google Scholar]
  41. Turner J. D., Le N. A., Brown W. V. Effect of changing dietary fat saturation on low-density lipoprotein metabolism in man. Am J Physiol. 1981 Jul;241(1):E57–E63. doi: 10.1152/ajpendo.1981.241.1.E57. [DOI] [PubMed] [Google Scholar]
  42. Wang H., Chen X., Fisher E. A. N-3 fatty acids stimulate intracellular degradation of apoprotein B in rat hepatocytes. J Clin Invest. 1993 Apr;91(4):1380–1389. doi: 10.1172/JCI116340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Windmueller H. G., Spaeth A. E. Regulated biosynthesis and divergent metabolism of three forms of hepatic apolipoprotein B in the rat. J Lipid Res. 1985 Jan;26(1):70–81. [PubMed] [Google Scholar]
  44. Wong S. H., Fisher E. A., Marsh J. B. Effects of eicosapentaenoic and docosahexaenoic acids on apoprotein B mRNA and secretion of very low density lipoprotein in HepG2 cells. Arteriosclerosis. 1989 Nov-Dec;9(6):836–841. doi: 10.1161/01.atv.9.6.836. [DOI] [PubMed] [Google Scholar]
  45. Wong S. H., Marsh J. B. Inhibition of apolipoprotein secretion and phosphatidate phosphohydrolase activity by eicosapentaenoic and docosahexaenoic acids in the perfused rat liver. Metabolism. 1988 Dec;37(12):1177–1181. doi: 10.1016/0026-0495(88)90197-7. [DOI] [PubMed] [Google Scholar]
  46. Wong S. H., Nestel P. J., Trimble R. P., Storer G. B., Illman R. J., Topping D. L. The adaptive effects of dietary fish and safflower oil on lipid and lipoprotein metabolism in perfused rat liver. Biochim Biophys Acta. 1984 Feb 9;792(2):103–109. doi: 10.1016/0005-2760(84)90209-1. [DOI] [PubMed] [Google Scholar]
  47. Wong S., Nestel P. J. Eicosapentaenoic acid inhibits the secretion of triacylglycerol and of apoprotein B and the binding of LDL in Hep G2 cells. Atherosclerosis. 1987 Apr;64(2-3):139–146. doi: 10.1016/0021-9150(87)90239-5. [DOI] [PubMed] [Google Scholar]
  48. von Lossonczy T. O., Ruiter A., Bronsgeest-Schoute H. C., van Gent C. M., Hermus R. J. The effect of a fish diet on serum lipids in healthy human subjects. Am J Clin Nutr. 1978 Aug;31(8):1340–1346. doi: 10.1093/ajcn/31.8.1340. [DOI] [PubMed] [Google Scholar]

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