Skip to main content
Log in

Liposomes as fatty acids carriers in isolated rat liver: effect on energy metabolism and on isolated mitochondria activity

  • Published:
Magnetic Resonance Materials in Physics, Biology and Medicine Aims and scope Submit manuscript

Abstract

The effects of fatty acids (FA)-carrier, egg-lecithin liposomes (LIPO) as alternative to BSA, on ATP, glycogen and glucose contents in isolated perfused liver of fed rats were non-invasively studied using31P/13C nuclear magnetic resonance (NMR). Oxidative phosohorylation was studied in isolated mitochondria from the same liver consecutively to the NMR experiments. ATP content decreased slowly and ATP turnover was similar during the perfusion with saline solution (KHB) or LIPO. However. LIPO induced an enhancement of respiratory control ratio in isolated mitochondria. Tissue glycogen and glucose content decreased when FA (linoleate or linolenate) were perfused with defatted BSA, (3%) or LIPO (600 mg/l) whereas glucose excretion level was unchanged and lactate excretion tended to increase, reflecting changes in the cytosolic redox state and/or an enhancement of glycolysis. Addition of FA (0.5 or 1.5 mM) to LIPO caused a dramatic fall in liver ATP, a mitochondrial uncoupling and an impairment of the phosphorylation activity. Perfusion with FA (1.5 mM) carried by BSA significantly increased the ATP degradation without change of mitochondrial function. Owing to the higher affinity of BSA than LIPO for FA, these latter could be more easily released from complex LIPO-FA, increasing their uncoupling effect. Hence, the FA concentrations have to be largely decreased from the above currently used concentrations to avoids this effect. It will then be possible to minimize the effector action of FA and to study their more specific metabolic function as fuel. It was concluded that LIPO were appropriate carriers to study the different metabolic effects of FA.

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

Access this article

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

BSA:

bovine serum albumin

EGTA:

ethylene glycol-bis (β-aminoethylether)N,N,N',N'-tetraacetic acid

FA:

Fatty acids

KHB:

Krebs-Henseleit bicarbonate medium

LIPO:

liposomes

MDPA:

methylene diphosphonic acid

NMR:

nuclear magnetic resonance

NTP:

nucleoside triphosphates

Pi:

inorganic phosphate

TES:

N-tris(hydroxymethyl)methyl-2-aminoethane-sulfonic acid

References

  1. Debeer LJ, Mannaerts G, de Schepper PJ. Effects of octanoate and oleate on energy metabolism in the perfused rat liver. Eur J Biochem 1974;47:591–600.

    Article  PubMed  CAS  Google Scholar 

  2. Williamson JR, Kreisberg RA, Felts PW. Mechanism for the stimulation of gluconeogenesis by fatty acids in perfused rat liver. Biochemistry 1966;56:247–54.

    CAS  Google Scholar 

  3. Scholz R, Schwabe U, Soboll S. Influence of fatty acids on energy metabolism. Stimulation of oxygen consumption, ketogenesis and CO2 production following addition of octanoate and oleate in perfused rat liver. Eur J Biochem 1984;141:223–30.

    Article  PubMed  CAS  Google Scholar 

  4. Diolez P, Moreau F. Correlations between ATP synthesis, membrane potential and oxidation rate in plant mitochondria. Physiol Plant 1986;59:177–82.

    Article  Google Scholar 

  5. Soboll S, Stucki J. Regulation of the degree of coupling of oxidative phosphorylation in intact rat liver. Biochim Biophys Acta 1985;807:245–54.

    Article  PubMed  CAS  Google Scholar 

  6. Rottenberg H, Hashimoto K. Fatty acid uncoupling of oxidative phosphorylation in rat liver mitochondria. Biochemistry 1986;25:1745–55.

    Article  Google Scholar 

  7. Vignais PV. Molecular and physiological aspects of adenine nucleotide transport in mitochondria. Biochim Biophys Acta 1976;456:1–38.

    PubMed  CAS  Google Scholar 

  8. Woldegiorgis G, Shrago E, Gipp J, Yatvin V. Fatty acyl coenzyme A-sensitive adenine nucleotide transport in a reconstituted liposome system. J Biol Chem 1981;256:12297–300.

    PubMed  CAS  Google Scholar 

  9. Spector AA. Fatty acid binding to plasma membrane. J Lipid Res 1975;16:165–79.

    PubMed  CAS  Google Scholar 

  10. Soboll S, Gründel S, Schwabe U, Scholz R. Influence of fatty acids on energy metabolism. Kinetics of changes in metabolic rates and changes in subcellular adenine nucleotide contents and pH gradients following addition of octanoate and oleate in perfused rat liver. Eur J Biochem 1984;141:231–6.

    Article  PubMed  CAS  Google Scholar 

  11. Soboll S, Seitz HJ, Sies H, Ziegler B, Scholz R: Effect of long chain fatty acyl-CoA on mitochondrial and cytosolic ATP/ADP ratios in the intact liver cell. Biochem J 1984;220:371–6.

    PubMed  CAS  Google Scholar 

  12. Krebs HA, Hems R. Fatty acid metabolism in the perfused rat liver. Biochem J 1970;119:525–33.

    PubMed  CAS  Google Scholar 

  13. Zhang ZJ, Wilcox HG, Elam MB, Casrellani LW, Heimberg M. Metabolism of n-3 polyunsaturated fatty acids by the isolated perfused rat liver. Lipids 1992;26:504–11.

    Article  Google Scholar 

  14. Soboll S, Scholz R, Heldt HW. Subcellular metabolite concentrations. Dependence of mitochondrial and cytosolic ATP systems on the metabolic state of perfused rat liver. Eur J Biochem 1978;87:377–90.

    Article  PubMed  CAS  Google Scholar 

  15. Dufour S, Rousse N, Canioni P, Diolez P. Top-down control analysis of temperature effect on oxidative phosphorylation. Biochem J 1996;314:743–51.

    PubMed  CAS  Google Scholar 

  16. Grundy SM. What is the desirable ratio of saturated, polyunsaturated, and monounsaturated fatty acids in the diet?. Am J Clin Nutr 1997;66:988S-90S.

    PubMed  CAS  Google Scholar 

  17. Feskens EJM, Virtanen SM, Räsänen L, et al. Dietary factors determining diabetes and impaired glucose tolerance. Diabetes Care 1995;18:1104–12.

    Article  PubMed  CAS  Google Scholar 

  18. Caggiula AW, Mustad VA. Effects of dietary fat and fatty acids on coronary artery disease risk and total and lipoprotein cholesterol concentrations: epidemiological studies. Am J Clin Nutr 1997;65:1597S-610S.

    PubMed  CAS  Google Scholar 

  19. Jensen MD. Diet effects on fatty acid metabolism in lean and obese humans. Am J Clin Nutr 1998;67:531–4.

    Google Scholar 

  20. Dufourq J, Faucon JF, Maget-Dana R, Pileni MP, Hélène C. A fluorescence study of the binding of oligopeptides containing aromatic and basic residues to phospholipid vesicles. Biochim Biophys Acta 1981;649:67–75.

    Article  Google Scholar 

  21. Pietri S, Bernard M, Cozzone PJ. Hydrodynamic and energetic aspects of exogenous free fatty acid perfusion in the isolated rat heart during high flow anoxia and reoxygenation: a31P magnetic resonance study. Cardiovasc Res 1991;25:398–406.

    PubMed  CAS  Google Scholar 

  22. Delmas-Beauvieux MC, Gallis JL, Rousse N, Clerc M, Canioni P: Phosphorous-31 nuclear magnetic resonance study of isolated rat liver during hypothermic ischemia and subsequent normothermic perfusion. J Hepatol 1992;15:192–201.

    Article  PubMed  CAS  Google Scholar 

  23. Gallis JL, Delmas-Beauvieux MC, Biran M, Rousse N, Durand T, Canioni P. Is cellular integrity responsible for the partial invisibility of ATP in isolated ischemic rat liver. NMR Biomed 1991;4:40–6.

    Article  Google Scholar 

  24. Dufour S, Gallis JL, Canioni P. P-31 NMR evaluation of ATP turnover in isolated perfused rat liver at 4°C. ISMRM 1993;2:1043.

    Google Scholar 

  25. Cannon B, Lindberg O. Mitochondria from brown adipose tissue: isolation and properties. Methods Enzymol 1979;55:65–78.

    Article  PubMed  CAS  Google Scholar 

  26. Leducq N, Delmas-Beauvieux MC, Bourdel-Marchasson I, et al. Mitochondrial permeability transition during hypothermic to normothermic reperfusion in rat liver demonstrated by the protective effect of cyclosporin A. Biochem J 1998;336:501–6.

    PubMed  CAS  Google Scholar 

  27. Canioni P, Alger JR, Shulman RG. Natural abundance C-13 NMR spectroscopy of liver and adipose tissue of the living rat. Biochemistry 1983;22:4974–80.

    Article  PubMed  CAS  Google Scholar 

  28. Noy N, Donnelly TM, Zakim D. Physical-chemical model for the entry of water-insoluble compounds into cells. Studies of fatty acid uptake by the liver. Biochemistry 1986;25:2013–21.

    Article  PubMed  CAS  Google Scholar 

  29. Cooper RB, Noy N, Zakim D. Mechanism for binding of fatty acids to hepatocyte plasma membranes. J Lipid Res 1989;30:1719–26.

    PubMed  CAS  Google Scholar 

  30. Scarbrough FE. Some food and drug administration perspectives of fat and fatty acids. Am J Clin Nutr 1997;65:1578S-80S.

    PubMed  CAS  Google Scholar 

  31. Kris-Etherton PM, Yu S. Individual fatty acids effects on plasma lipids and lipoproteins: human studies. Am J Clin Nutr 1997;65:1628S-44S.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Delmas-Beauvieux, M.C., Leducq, N., Thiaudière, E. et al. Liposomes as fatty acids carriers in isolated rat liver: effect on energy metabolism and on isolated mitochondria activity. MAGMA 10, 43–51 (2000). https://doi.org/10.1007/BF02613111

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02613111

Keywords

Navigation