Skip to main content
SpringerLink
Log in

Surface composition regulates clearance from plasma and triolein lipolysis of lipid emulsions

  • Published:
Lipids

Abstract

Sphingomyelin (SM) and cholesterol (Chol) are major surface lipid constituents of plasma lipoproteins. We investigated the effects of SM and Chol on the plasma clearance of lipid emulsions as a model for lipoprotein particles in rats. The presence of Chol facilitated the removal of emulsion particles from plasma, whereas SM delayed particle removal. Preinjection of lactoferrin, an inhibitor of the apolipoprotein E (apoE) receptor, revaled that the differences in clearance of emulsions were due to the differences in affinity for the apoE receptor. Measurement of apolipoprotein binding suggested that the balance of apoE and apoC (apoC-II and apoC-III) bound to emulsions caused the difference in plasma clearance of emulsion particles. That is to say, SM in the emulsion surface decreased binding of apoE, which led to a longer circulation of emulsion particles in plasma. Chol, on the other hand, decreased the ratio of apoC to apoE, which may have promoted emulsion uptake through the apoE receptor. We also examined in vitro lipolysis using immobilized lipoprotein lipase (LPL) in a heparin affinity column. Lipolysis rates were significantly reduced by the incorporation of SM into the emulsion surface, but not by the incorporation of Chol, indicating that SM in the lipoprotein surface is an important lipid component regulating LPL-mediated lipolysis. Our results suggest that the presence of SM and Chol in the lipoprotein surface plays an important role in the circulation behavior and LPL-mediated lipolysis of lipid emulsions through their effect on the selectivity of plasma protein binding.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

apoC:

summary term for apoC-II and apoC-III

apoC-II:

apolipoprotein C-II

apoC-III:

apolipoprotein C-III

apoE:

apolipoprotein E

Chol:

cholesterol

FFA:

free fatty acids

LPL:

lipoprotein lipase

PC:

phosphatidylcholine

SM:

sphingomyelin

TG:

triacylglycerol

TO:

triolein

References

  1. Mizushima, Y., and Hoshi, K. (1993) Recent Advances in Lipid Microsphere Technology for Targeting Prostaglandin Delivery, J. Drug Target 1, 93–100.

    PubMed  CAS  Google Scholar 

  2. Otomo, S., Mizushima, Y., Aihara, H., Yokoyama, K., Watanabe, M., and Yanagawa, A. (1985) Prostaglandin E1 Incorporated in Lipid Microspheres (Lipo PGE1) Drugs Exp. Clin. Res. 11, 627–631.

    PubMed  CAS  Google Scholar 

  3. Yamaguchi, T., Fukushima, Y., Itai, S., and Hayashi, H. (1995) Rate of Release and Retentivity of Prostaglandin E1 in Lipid Emulsion, Biochim. Biophys. Acta 1256, 381–386.

    PubMed  Google Scholar 

  4. Hultin, M., Carneheim, C., Rosenqvist, K., and Olivecrona, T. (1995) Intravenous Lipid Emulsions: Removal Mechanisms as Compared to Chylomicrons, J. Lipid Res. 36, 2174–2184.

    PubMed  CAS  Google Scholar 

  5. Maranhao, R.C., Tercyak, A.M., and Redgrave, T.G. (1986) Effects of Cholesterol Content on the Metabolism of Protein-Free Emulsion Models of Lipoproteins, Biochim. Biophys. Acta 875, 247–255.

    PubMed  CAS  Google Scholar 

  6. Kowal, R.C., Herz, J., Weisgraber, K.H., Mahley, R.W., Brown, M.S., and Goldstein, J.L. (1990) Opposing Effects of Apolipoproteins E and C on Lipoprotein Binding to Low Density Lipoprotein Receptor-Related Protein, J. Biol. Chem. 265, 10771–10779.

    PubMed  CAS  Google Scholar 

  7. Swaney, J.B., and Weisgraber, K.H. (1994) Effect of Apo-lipoprotein C-I Peptides on the Apolipoprotein E Content and Receptor-Binding Properties of Beta-Migrating Very Low Density Lipoproteins, J. Lipid Res. 35, 134–142.

    PubMed  CAS  Google Scholar 

  8. Sehayek, E., and Eisenberg, S. (1991) Mechanisms of Inhibition by Apolipoprotein C of Apolipoprotein E-Dependent Cellular Metabolism of Human Triglyceride-Rich Lipoproteins Through the Low Density Lipoprotein Receptor Pathway, J. Biol. Chem. 266, 18259–18267.

    PubMed  CAS  Google Scholar 

  9. Windler, E., Chao, Y.-s., and Havel, R.J. (1980) Regulation of the Hepatic Uptake of Triglyceride-Rich Lipoproteins in the Rat. Opposing Effects of Homologous Apolipoprotein E and Individual C Apoproteins, J. Biol. Chem. 255, 8303–8307.

    PubMed  CAS  Google Scholar 

  10. Windler, E., and Havel, R.J. (1985) Inhibitory Effects of C Apolipoproteins from Rats and Humans on the Uptake of Triglyceride-Rich Lipoproteins and Their Remnants by the Perfused Rat Liver, J. Lipid Res. 26, 556–565.

    PubMed  CAS  Google Scholar 

  11. Weisgraber, K.H., Mahley, R.W., Kowal, R.C., Herz, J., Goldstein, J.L., and Brown, M.S. (1990) Apolipoprotein C-I Modulates the Interaction of Apolipoprotein E with β-Migrating Very Low Density Lipoproteins (β-VLDL) and Inhibits Binding of β-VLDL to Low Density Lipoprotein Receptor-Related Protein, J. Biol. Chem. 265, 22453–22459.

    PubMed  CAS  Google Scholar 

  12. Osborne, J.C.J., Bengtsson Olivecrona, G., Lee, N.S., and Olivecrona, T. (1985) Studies on Inactivation of Lipoprotein Lipase: Role of the Dimer to Monomer Dissociation, Biochemistry 24, 5606–5611.

    Article  PubMed  CAS  Google Scholar 

  13. Cooper, A.D. (1997) Hepatic Uptake of Chylomicron Remnants, J. Lipid Res. 38, 2173–2192.

    PubMed  CAS  Google Scholar 

  14. Miller, K.W., and Small, D.M. (1983) Surface-to-Core and Interparticle Equilibrium Distributions of Triglyceride-Rich Lipoprotein Lipids, J. Biol. Chem. 258, 13772–13784.

    PubMed  CAS  Google Scholar 

  15. Ben Yashar, V., and Barenholz, Y. (1991) Characterization of the Core and Surface of Human Plasma Lipoproteins. A Study Based on the Use of Five Fluorophores, Chem. Phys. Lipids 60, 1–14.

    Article  PubMed  CAS  Google Scholar 

  16. Subbaiah, P.V., Davidson, M.H., Ritter, M.C., Buchanan, W., and Bagdade, J.D. (1989) Effects of Dietary Supplementation with Marine Lipid Concentrate on the Plasma Lipoprotein Composition of Hypercholesterolemic Patients, Atherosclerosis 79, 157–166.

    Article  PubMed  CAS  Google Scholar 

  17. Subbaiah, P.V., and Liu, M. (1993) Role of Sphingomyelin in the Regulation of Cholesterol Esterification in the Plasma Lipoproteins. Inhibition of Lecithin-Cholesterol Acyltransferase Reaction. J. Biol. Chem. 268, 20156–20163.

    PubMed  CAS  Google Scholar 

  18. Windler, E.E., Preyer, S., and Greten, H. (1986) Influence of Lysophosphatidylcholine on the C-Apolipoprotein Content of Rat and Human Triglyceride-Rich Lipoproteins During Triglyceride Hydrolysis, J. Clin. Invest. 78, 658–665.

    PubMed  CAS  Google Scholar 

  19. Gupta, A.K., and Rudney, H. (1992) Sphingomyelinase Treatment of Low Density Lipoprotein and Cultured Cells Results in Enhanced Processing of LDL Which Can Be Modulated by Sphingomyelin, J. Lipid Res. 33, 1741–1752.

    PubMed  CAS  Google Scholar 

  20. Saito, H., Nishiwaki, K., Handa, T., Ito, S., and Miyajima, K. (1995) Comparative Study of Fluorescence Anisotropy in Surface Monolayers of Emulsions and Bilayers of Vesicle, Langmuir 11, 3742–3747.

    Article  CAS  Google Scholar 

  21. Bartlett, G.R. (1959) Phosphorus Assay in Column Chromatography, J. Biol. Chem. 234, 466–468.

    PubMed  CAS  Google Scholar 

  22. Saito, H., Minamida, T., Arimoto, I., Handa, T., and Miyajima, K. (1996) Physical States of Surface and Core Lipids in Lipid Emulsions and Apolipoprotein Binding to the Emulsion Surface, J. Biol. Chem. 271, 15515–15520.

    Article  PubMed  CAS  Google Scholar 

  23. Arimoto, I., Saito, H., Kawashima, Y., Miyajima, K., and Handa, T. (1998) Effects of Sphingomyelin and Cholesterol on Lipoprotein Lipase-Mediated Lipolysis in Lipid Emulsions, J. Lipid Res. 39, 143–151.

    PubMed  CAS  Google Scholar 

  24. Callow, M.J., Mortimer, B.C., and Redgrave, T.G. (1993) Charge Effects on Chylomicron Clearance in Rats, Biochem. Mol. Biol. Int. 29, 913–919.

    PubMed  CAS  Google Scholar 

  25. van Dijk, M.C., Ziere, G.J., Boers, W., Linthorst, C., Bijsterbosch, M.K., and van Berkel, T.J. (1991) Recognition of Chylomicron Remnants and β-Migrating Very Low Density Lipoproteins by the Remnant Receptor of Parenchymal Liver Cells Is Distinct from the Liver Alpha 2-Macroglobulin-Recognition Site, Biochem. J. 279, 863–870.

    PubMed  Google Scholar 

  26. Rensen, P.C., van Dijk, M.C., Havenaar, E.C., Bijsterbosch, M.K., Kruijt, J.K., and van Berkel, T.J. (1995) Selective Liver Targeting of Antivirals by Recombinant Chylomicrons—A New Therapeutic Approach to Hepatitis B [See Comments], Nat. Med. 1, 221–225.

    Article  PubMed  CAS  Google Scholar 

  27. Huettinger, M., Retzek, H., Eder, M., and Goldenberg, H. (1988) Characteristics of Chylomicron Remnant Uptake into Rat Liver, Clin. Biochem. 21.

  28. Férézou, J., Nguyen, T.L., Leray, C., Hajri, T., Frey, A., Cabaret, Y., Courtieu, J., Lutton, C., and Bach, A.C. (1994) Lipid Composition and Structure of Commercial Parenteral Emulsions, Biochim. Biophys. Acta 1213, 149–158.

    PubMed  Google Scholar 

  29. Hajri, T., Ferezou, J., and Lutton, C. (1990) Effects of Intravenous Infusions of Commercial Fat Emulsions (Intralipid 10 or 20%) on Rat Plasma Lipoproteins: Phospholipids in Excess Are the Main Precursors of Lipoprotein-X-Like Particles, Biochim. Biophys. Acta 1047, 121–130.

    PubMed  CAS  Google Scholar 

  30. Komatsu, H., Handa, T., and Miyajima, K. (1994) Comparative Estimation of the Liposomal Content of Phosphatidylcholine Triolein Emulsions Using Fluorescence Quenching and H NMR, Chem. Pharm. Bull. 42, 1715–1719.

    CAS  Google Scholar 

  31. Rotenberg, M., Rubin, M., Bor, A., Meyuhas, D., Talmon, Y., and Lichtenberg, D. (1991) Physicochemical Characterization of Intralipid Emulsions, Biochim. Biophys. Acta 1086, 265–272.

    PubMed  CAS  Google Scholar 

  32. Westesen, K., and Wehler, T. (1992) Physicochemical Characterization of a Model Intravenous Oil-in-Water Emulsion, J. Pharm. Sci. 81, 777–786.

    Article  PubMed  CAS  Google Scholar 

  33. Handa, T., Saito, H., and Miyajima, K. (1990) Phospholipid Monolayers at the Triolein-Saline Interface: Production of Microemulsion Particles and Conversion of Monolayers to Bilayers, Biochemistry 29, 2884–2890.

    Article  PubMed  CAS  Google Scholar 

  34. Redgrave, T.G., Vassiliou, G.G., and Callow, M.J. (1987), Cholesterol Is Necessary for Triacylglycerol-Phospholipid Emulsions to Mimic the Metabolism of Lipoproteins, Biochim. Biophys. Acta 921, 154–157.

    PubMed  CAS  Google Scholar 

  35. Handa, T., Eguchi, Y., and Miyajima, K. (1994) Effects of Cholesterol and Cholesteryl Oleate on Lipolysis and Liver Uptake of Triglyceride/Phosphatidylcholine Emulsions in Rats, Pharm. Res. 11, 1283–1287.

    Article  PubMed  CAS  Google Scholar 

  36. Jackson, R.L., Tajima, S., Yamamura, T., Yokoyama, S., and Yamamoto, A. (1986) Comparison of Apolipoprotein C-II-Deficient Triacylglycerol-Rich Lipoproteins and Trioleoylglycerol/Phosphatidylcholine-Stabilized Particles as Substrates for Lipoprotein Lipase, Biochim. Biophys. Acta 875, 211–219.

    PubMed  CAS  Google Scholar 

  37. Tajima, S., Yokoyama, S., and Yamamoto, A. (1984) Mechanism of Action of Lipoprotein Lipase on Triolein Particles: Effect of Apolipoprotein C-II, J. Biochem. 96, 1753–1767.

    PubMed  CAS  Google Scholar 

  38. Wang, C.S., McConathy, W.J., Kloer, H.U., and Alaupovic, P. (1985) Modulation of Lipoprotein Lipase Activity by Apolipoproteins. Effect of Apolipoprotein C-III, J. Clin. Invest. 75, 384–390.

    Article  PubMed  CAS  Google Scholar 

  39. Andersson, Y., Lookene, A., Shen, Y., Nilsson, S., Thelander, L., and Olivecrona, G. (1997) Guinea Pig Apolipoprotein C-II: Expression in E. coli, Functional Studies of Recombinant Wild-Type and Mutated Variants, and Distribution on Plasma Lipoproteins, J. Lipid Res. 38, 2111–2124.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Osaka Branch, National Institute of Health Sciences, 540, Osaka, Japan

    Hiroyuki Saito

  2. Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, 606-8501, Kyoto, Japan

    Itaru Arimoto, Chizuko Matsumoto, Masafumi Tanaka, Keiichirou Okuhira & Tetsurou Handa

Authors
  1. Itaru Arimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chizuko Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masafumi Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Keiichirou Okuhira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroyuki Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tetsurou Handa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tetsurou Handa.

About this article

Cite this article

Arimoto, I., Matsumoto, C., Tanaka, M. et al. Surface composition regulates clearance from plasma and triolein lipolysis of lipid emulsions. Lipids 33, 773–779 (1998). https://doi.org/10.1007/s11745-998-0269-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-998-0269-8

Keywords

Search

Navigation