Journal Mobile Options
Table of Contents
Vol. 49, No. 6, 2005
Issue release date: November–December 2005
Ann Nutr Metab 2005;49:397–406

Comparative Effect of Fish Oil Feeding and Other Dietary Fatty Acids on Plasma Lipoproteins, Biliary Lipids, and Hepatic Expression of Proteins Involved in Reverse Cholesterol Transport in the Rat

Morgado N. · Rigotti A. · Valenzuela A.
aLaboratorio de Lípidos y Antioxidantes, INTA, Universidad de Chile, and bDepartamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background: While elevated plasma high-density lipoprotein (HDL) levels has been associated to a reduction in cardiovascular risk, dietary fish oils rich in omega–3 polyunsaturated fatty acids (PUFAs) may protect against this disease. The protective effect of HDL is associated to its participation in the reverse cholesterol transport pathway. On the other hand, omega–3 PUFAs decrease plasma HDL levels compared to other fatty acids, which may suggest an effect on reverse cholesterol transport. Aim: In this work, the effect of dietary fish oil on the fatty acid composition of hepatic membranes, plasma lipoprotein cholesterol profile, biliary lipids, and the expression of proteins involved in reverse cholesterol transport, was compared to other dietary oils having a different degree of fatty acid unsaturation. Methods: Male rats were fed a semi synthetic diet containing fish oil (omega–3), sunflower oil (omega–6), olive oil (omega–9) or coconut oil (saturated). Hepatic membrane fatty acid composition, plasma cholesterol levels, lipoprotein cholesterol profile, biliary lipids, hepatic mRNA levels for lecithin cholesterol acyltransferase, hepatic lipase, apo E, and apo A-I, and hepatic protein levels of the scavenger receptor class B type I, caveolin-1, and the ATP binding cassette transporter A1 were analyzed. Plasma apo A-I and apo E protein levels were also evaluated. Results: Compared to the other diets, omega–3 PUFAs significantly changed omega–3/omega–6 fatty acid ratio of hepatic membranes, caused a reduction of plasma total and HDL cholesterol, and selectively increased biliary cholesterol secretion. No modification in the expression levels of lecithin cholesterol acyltransferase, hepatic lipase, apo A-I and apo E mRNA was observed. Hepatic scavenger receptor class B type I, caveolin-1, and the ATP binding cassette transporter A1 protein levels were also not affected. Plasma apo A-I, but not apo E, was reduced. Conclusions: These results show that dietary omega–3 PUFAs reduce plasma HDL cholesterol and increase biliary cholesterol without concomitant modifications in the expression of key genes and proteins involved in reverse cholesterol transport. These findings suggest that functional changes in the activity of these proteins as consequence of the incorporation of omega-3 PUFAs into hepatic membranes and plasma lipoproteins may underlie the effect of fish oil feeding on plasma and hepatic cholesterol metabolism in the rat.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Ascherio A, Rimm E, Stampfer M, Giovanucci E, Willet W: Dietary intake of marine n–3 fatty acids, fish intake, and the risk of coronary disease among men. N Engl J Med 1995;332:977–982.
  2. Hargreaves A, Logan R, Thomson M, Elton R, Oliver M, Riemersma R: Total cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol and coronary heart disease in Scotland. BMJ 1991;303:678–681.
  3. Tall A: Plasma high density lipoproteins: Metabolism and relationship to atherogenesis. J Clin Invest 1990;86:279–284.
  4. Von Eckardstein A, Nofer J, Assmann G: High density lipoproteins and arteriosclerosis: Role of cholesterol efflux and reverse cholesterol transport. Arterioscler Thromb Vasc Biol 2001;21:13–27.
  5. Sviridov D, Nestel P: Dynamics of reverse cholesterol transport: Protection against atherosclerosis. Atherosclerosis 2002;161:245–254.
  6. Kullak-Ublick G, Beuers U, Paumgartner G: Hepatobiliary transport. J Hepatol 2003;32(suppl):3–18.
  7. Hu F, Manson J, Willet W: Types of dietary fat and risk of coronary heart disease: A critical review. J Am Coll Nutr 2001;1:5–19.
  8. Hu F, Stampfer M, Manson J, Ascherio A, Colditz G, Speizer F, Hennekens C, Willet W: Dietary saturated fat and their food sources in relation to the risk of coronary heart disease in women. Am J Clin Nutr 1999;70:1001–1008.
  9. Nicolosi R: Dietary fat saturation effects on low-lipoprotein concentrations and metabolism in various animal models. Am J Clin Nutr 1997;65(suppl):1617s–1627s.
  10. Griffin B: The effect of omega–3 fatty acids on low density lipoprotein subfractions. Lipids 2001;36(suppl):s91–s97.

    External Resources

  11. Thornberg J, Rudel L: How do polyunsaturated fatty acids lower lipids. Curr Opin Lipidol 1992;3:17–21.

    External Resources

  12. Mensink R, Katan M: Effect of a diet enriched with monounsaturated or polyunsaturated fatty acids on levels of low-density and high-density lipoprotein cholesterol in healthy women and men. N Engl J Med 1989;17:436–441.
  13. Khosla P, Sundram K: Effects of dietary fatty acids composition on plasma cholesterol. Prog Lipid Res 1996;35:93–122.
  14. Nestel P: Effects of n–3 fatty acids on lipid metabolism. Annu Rev Nutr 1990;10:149–167.
  15. Montoya M, Porres A, Serrano S, Fruchart J, Mata P, Gómez J, Castro G: Fatty acid saturation on the diet and plasma lipid concentrations, lipoprotein particle concentrations, and cholesterol efflux capacity. Am J Clin Nutr 2002;75:484–491.
  16. Fielding C, Fielding E: Molecular physiology of reverse cholesterol transport. J Lipid Res 1995;9:155–167.
  17. Bodzioch-Wilson A, Klucken J, Langmann T, Bottchert A, Diederich W, Drobnick W, Barlage S, Buchler C, Porch-Ozcurumez M, Kaminski W, Hahmann H, Oette K, Rothe G, Aslanidis C, Lackner K, Schmitz G: The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease. Nat Genet 1999;22:347–351.
  18. Glomset J, Janssen E, Kennedy R, Dobbins J: Role of plasma lecithin: Cholesterol acyltransferase in the metabolism of high density lipoproteins. J Lipid Res 1966;7:639–648.
  19. Fielding P, Nagao K, Hakamata H, Chimini G, Fielding C: A two step mechanism for free cholesterol and phospholipid efflux for human vascular cells to apolipoprotein A-1. Biochemistry 2000;39:14113–14120.
  20. Acton S, Rigotti A, Landshulz K, Xu Sh, Hobbs H, Krieger M: Identification of scavenger receptor SR-BI high density lipoprotein receptor. Science 1996;271:518–520.
  21. Rigotti A, Trigatti B, Penman M, Rayburn H, Herz J, Krieger M: A targeted mutation in the murine gene encoding the high density lipoprotein (HDL) receptor scavenger receptor class B type I reveals its key role in HDL metabolism. Proc Natl Acad Sci USA 1997;94:12610–12615.
  22. Kozarsky K, Donahee M, Rigotti A, Iqbal S, Edelman E, Krieger, M: Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels. Nature 1997;387:414–417.
  23. Mardones P, Quiñones V, Amigo L, Moreno M, Miquel JF, Schwarz M, Miettinen H, Rigatti B, Krieger M, Van Patten S, Cohen D, Rigotti A: Hepatic cholesterol and bile acid metabolism and intestinal cholesterol absorption in scavenger receptor class B type I-deficient mice. J Lipid Res 2001;42:170–180.
  24. Quest AF, Leyton L, Parraga M: Caveolins, caveolae, and lipid rafts in cellular transport, signaling, and disease. Biochem Cell Biol 2004;82:129–144.
  25. Frank PG, Marcel YL, Connelly MA, Lublin DM, Franklin V, Williams DL, Lisanti MP: Stabilization of caveolin-1 by cellular cholesterol and scavenger receptor class B type I. Biochemistry 2002;41:11931–11940.
  26. Barrans A, Collet X, Barbaras R, Jaspard B, Manent J, Vieu C, Chap H, Perret B: Hepatic lipase induces the formation of pre-beta 1 high density lipoprotein (HDL) from triacylglycerol-rich HDL2: A study comparing liver perfusion to in vitro incubation with lipases. J Biol Chem 1994;269:11572–11577.
  27. Wang N, Weng W, Breslow J, Tall A: Scavenger receptor BI (SR-BI) is up-regulated in adrenal gland in apolipoprotein A-I and hepatic lipase knock-out mice as a response to depletion of cholesterol stores. In vivo evidence that SR-BI is a functional high density lipoprotein receptor under feedback control. J Biol Chem 1996;271:21001–21004.
  28. Lapillonne A, Clarke SD, Heird W: Polyunsaturated fatty acids and gene expression. Curr Opin Clin Nutr Metab Care 2004;7:151–156.
  29. Clarke S, Jump D: Dietary polyunsaturated fatty acid regulation of gene transcription Annu Rev Nutr 1994;14:83–98.
  30. Clamp G, Ladha S, Clark D, Grimble R, Lund EK: The influence of dietary lipids on the composition and membrane fluidity of rat hepatocyte plasma membrane. Lipids 1997;32:179–184.
  31. Schachter D: Fluidity and function of hepatocyte plasma membranes. Hepatology 1984;4:140–151.
  32. Kinsella J: Lipids, membrane receptors, and enzymes: Effects of dietary fatty acids. J Parenter Enteral Nutr 1990;14(suppl):200S–217S.

    External Resources

  33. Fungwe T, Kudchodkar B, Lacko A, Dory L: Fatty acids modulate lecithin:cholesterol acyltransferase secretion independently of effects on triglyceride secretion in primary rat hepatocytes. J Nutr 1998;128:1270–1275.
  34. Loison C, Mendy F, Serougne C, Lutton C: Dietary myristic acid modifies the HDL-cholesterol concentration and liver scavenger receptor BI expression in the hamster. Br J Nutr 2002;87:199–210.
  35. Hatahet W, Cole L, Kudchodkar BJ, Fungwe T: Dietary fats differentially modulate the expression of lecithin: Cholesterol acyltransferase, apoprotein-A1 and scavenger receptor B1 in rats. J Nutr 2003;133:689–694.
  36. Spady D, Kearney D, Hobbs H: Polyunsaturated fatty acids up-regulate hepatic scavenger receptor B1 (SR-BI) expression and HDL cholesteryl ester uptake in the hamster. J Lipid Res 1999;40:1384–1394.
  37. le Morvan V, Dumon MF, Palos-Pinto A, Berard A: n–3 FA increase liver uptake of HDL-cholesterol in mice. Lipids 2002;37:767–772.
  38. Saito M, Oh-Hashi A, Kubota M, Nishide E, Yamaguchi M: Mixed function oxidases in response to different types of dietary lipids in rats. Br J Nutr 1990;63:249–257.
  39. Bligh E, Dyer W: A rapid method for total lipid extraction and purification. Can J Physiol 1959;37:911–917.
  40. Morrison W, Smith L: Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride-methanol. J Lipid Res 1964;5:600–608.
  41. Turley S, Dietschy J: Re-evaluation of the 3-alpha-hydroxysteroid dehydrogenase assay for total bile acids in bile. J Lipid Res 1978;19:924–928.
  42. Lowry O, Rosebrough N, Farr A, Randall R: Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–275.
  43. Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:156–159.
  44. Harris W, Connor W, Illingworth D, Rothrock D, Foster D: Effects of fish oil on VLDL triglyceride kinetics in humans. J Lipid Res 1990;31:1549–1558.
  45. Balasubramaniam S, Simoms L, Chang S, Hickie J: Reduction in plasma cholesterol and increase in biliary cholesterol by a diet rich in n–3 fatty acids in rat. J Lipid Res 1985;26:684–689.
  46. Smit M, Verkade H, Havinga R, Vonk R, Scherphof G, In´t Veld G, Kuipers F: Dietary fish oil potentiates bile-acid induced cholesterol secretion into bile in rats. J Lipid Res 1994;35:301–310.
  47. Botman K, Bravo E: The role of lipoprotein cholesterol in biliary steroid secretion. Studies with in vivo experimental models. Prog Lipid Res 1995;34:71–97.
  48. Kramer J, LeDeaux J, Butteiger D, Young T, Crankshaw C, Harlow H, Kier L, Ganeh Bath B: Transcription profiling in rat liver in response to dietary docosahexaenoic acid implicates stearoyl-coenzyme A desaturase as a nutritional target for lipid lowering. J Nutr 2003;133:57–66.
  49. Hashimoto M, Hossain M, Shimada T, Yamasaki H, Fujii Y, Shido O: Effects of docosahexaenoic acid on annular lipid fluidity on the rat bile canalicular plasma membrane. J Lipid Res 2001;42:1160–1168.
  50. Asamoto Y, Tazuma S, Ochi H, Chayama K, and Suzuki H: Bile-salt hydrophobicity is a key factor regulating rat liver plasma-membrane communication: Relation to bilayer structure, fluidity and transporter expression and function Biochem J 2001;359:605–610.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50