Skip to main content
SpringerLink
Log in

Erucic Acid is Differentially Taken up and Metabolized in Rat Liver and Heart

  • Original Article
  • Published:
Lipids

Abstract

Because X-linked adrenoleukodystrophy is treated using erucic acid (22:1n-9), we assessed its metabolism in rat liver and heart following infusion of [14-14C]22:1n-9 (170 Ci/kg) under steady-state-like conditions. In liver, 2.3-fold more tracer was taken up as compared to heart, accounted entirely by increased incorporation into the organic fraction (4.2-fold). The amount of tracer entering the aqueous fraction, which represents β-oxidation, was not different between groups; however a significantly elevated proportion of tracer was in the heart aqueous fraction. In both tissues, 76% of the radioactivity found in the organic fraction was esterified in neutral lipids, while only about 10% was found esterified into phospholipids. In liver, 56% of lipid radioactivity was found in cholesteryl esters, whereas in heart 64% was found in triacylglycerols. Because 22:1n-9 can be chain shortened, we assessed tracer metabolism using phenacyl fatty acid derivatives esterified from saponified esterified neutral lipid (triacylglycerol/cholesteryl ester) and phospholipid fractions. In heart esterified neutral lipids, 75% of tracer was recovered as 22:1n-9 and only 10% as oleic acid (18:1n-9), while in liver only 25% of the tracer was recovered as 22:1n-9, while 50% was found as stearic acid (18:0) and 10% as 18:1n-9. In liver and heart phospholipids, the tracer was distributed amongst the n-9 fatty acid family. Thus, 22:1n-9 under went tissue selective metabolism, with conversion to 18:0 the dominant pathway in the liver presumably for export in the neutral lipids, while in heart it was found primarily as 22:1n-9 in neutral lipids and used for β-oxidation.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

BBB:

Blood brain barrier

CE:

Cholesteryl esters

CerPCho:

Sphingomyelin

ChoGpl:

Choline glycerophospholipids

CNS:

Central nervous system

EtnGpl:

Ethanolamine glycerophospholipids

FFA:

Free fatty acids

PL:

Phospholipids

PtdIns:

Phosphatidylinositol

PtdSer:

Phosphatidylserine

SFA:

Saturated fatty acids

TAG:

Triacylglycerols

VLCFA:

Very-long-chain saturated fatty acids

X-ALD:

X-linked adrenoleukodystrophy

16:0:

Palmitic acid

18:0:

Stearic acid

18:1n-9:

Oleic acid

20:4n-6:

Arachidonic acid

22:1n-9:

Erucic acid

References

  1. Moser HW, Moser AB, Frayer KK, Chen W, Schulman JD, O’Neill BP, Kishimoto Y (1981) Adrenoleukodystrophy: increased plasma content of saturated very long chain fatty acids. Neurology 31:1241–1249

    PubMed  CAS  Google Scholar 

  2. Igarashi M, Schaumburg HH, Powers J, Kishimoto Y, Kolodny E, Suzuki K (1976) Fatty acid abnormality in adrenoleukodystrophy. J Neurochem 26:851–860

    Article  PubMed  CAS  Google Scholar 

  3. Theda C, Moser AB, Powers JM, Moser HW (1992) Phospholipids in X-linked adrenoleukodystrophy white matter-fatty acid abnormalities before the onset of demyelination. J Neurol Sci 110:195–204

    Article  PubMed  CAS  Google Scholar 

  4. Dubois-Dalcq M, Feigenbaum V, Aubourg P (1999) The neurobiology of X-linked adrenoleukodystrophy, a demyelinating peroxisomal disorder. Trends Neurosci 22:4–12

    Article  PubMed  CAS  Google Scholar 

  5. Wilson R, Sargent JR (1993) Lipid and fatty acid composition of brain tissue from adrenoleukodystrophy patients. J Neurochem 61:290–297

    Article  PubMed  CAS  Google Scholar 

  6. Paintlia AS, Gilg AG, Khan M, Signh AK, Barbosa E, Singh I (2003) Correlation of very long chain fatty acid accumulation and inflammatory disease progression in childhood X-ALD implications for potential therapies. Neurobiol Dis 14:425–439

    Article  PubMed  CAS  Google Scholar 

  7. Rizzo WB, Leshner RT, Odone A, Dammann AL, Craft DA, Jensen ME, Jennings SS, Davis S, Jaitly R, Sgro JA (1989) Dietary erucic acid therapy for X-linked adrenoleukodystrophy. Neurology 39:1415–1422

    PubMed  CAS  Google Scholar 

  8. Kaplan PW, Tusa RJ, Shankroff J, Heller J, Moser HW (1993) Visual evoked potentials in adrenoleukodystrophy: a trial with glycerol trioleate and Lorenzo oil. Ann Neurol 34:169–174

    Article  PubMed  CAS  Google Scholar 

  9. Odone A, Odone M (1989) Lorenzo’s oil a new treatment for adrenoleukodystrophy. J Pediatr Neurosci 5:55–61

    Google Scholar 

  10. Rasmussen M, Moser AB, Borel J, Khangoora S, Moser HW (1994) Brain, liver, and adipose tissue erucic and very long chain fatty acid levels in adrenoleukodystrophy patients treater with glyceryl trierucate and trioleate oils (Lorenzo’s oil). Neurochem Res 19:1073–1082

    Article  PubMed  CAS  Google Scholar 

  11. Poulos A, Gibson R, Sharp P, Beckman K, Grattan-Smith P (1994) Very long chain fatty acids in X-linked adrenoleukodystrophy brain after treatment with Lorenzo’s oil. Ann Neurol 36:741–746

    Article  PubMed  CAS  Google Scholar 

  12. Moser HW, Raymond GV, Koehler W, Sokolowski P, Hanefeld F, Korenke GC, Green A, Loes DJ, Hunneman DH, Jones RO, Lu S-E, Uziel G, Blasco MLG, Roels F (2003) Evaluation of the preventive effect of glyceryl trioleate-trierucate (“Lorenzo’s oil”) therapy in X-linked adrenoleukodystrophy: results of two concurrent trials. Adv Exp Med Biol 544:369–387

    PubMed  CAS  Google Scholar 

  13. Moser HW, Raymond GV, Lu S-E, Muenz LR, Moser AB, Xu J, Jones RO, Loew DJ, Melhem ER, Dubey P, Bezman L, Brereton NH, Odone A (2005) Follow-up of 89 asymptomatic patients with adrenoleukodystrophy treated with Lorenzo’s oil. Arch Neurol 62:1073–1080

    Article  PubMed  Google Scholar 

  14. Ferri R, Chance PF (2005) Lorenzo’s oil: advances in the treatment of neurometabolic disorders. Arch Neurol 62:1045–1046

    Article  PubMed  Google Scholar 

  15. Golovko MY, Murphy EJ (2006) Uptake and metabolism of plasma derived euricic acid by rat brain. J Lipid Res 47:1289–1297

    Article  PubMed  CAS  Google Scholar 

  16. Kramer JKG, Farnworth ER, Johnston KM, Wolynetz MS, Modler HW, Sauer FD (1990) Myocardial changes in newborn piglets fed sow milk or milk replacer diets containing different levels of erucic acid. Lipids 25:729–737

    Article  PubMed  CAS  Google Scholar 

  17. Kramer JKG, Sauer FD, Wolynetz MS, Farnworth ER, Johnston KM (1992) Effects of dietary saturated fat on erucic acid induced myocardial lipidosis in rats. Lipids 27:619–623

    Article  PubMed  CAS  Google Scholar 

  18. Norseth J, Christophersen BO (1978) Chain shortening of erucic acid in isolated liver cells. FEBS Lett 88:353–357

    Article  PubMed  CAS  Google Scholar 

  19. Christiansen RZ, Christiansen EN, Bremer J (1979) The stimulation of erucate metabolism in isolated rat hepatocytes by rapeseed oil and hydrogenated marine oil-containing diets. Biochim Biophys Acta 573:417–429

    PubMed  CAS  Google Scholar 

  20. Rogers CG (1977) Lipid composition and erucic acid in rat liver cells in culture. Lipids 12:1043–1049

    Article  PubMed  CAS  Google Scholar 

  21. Pinson A, Padieu P (1974) Erucic acid oxidation by beating heart cells in culture. FEBS Lett 39:88–90

    Article  PubMed  CAS  Google Scholar 

  22. Sauer FD, Kramer JKG, Forester GV, Butler KW (1989) Palmitic and erucic acid metabolism in isolated perfused hearts from weanling pigs. Biochim Biophys Acta 1004:205–214

    PubMed  CAS  Google Scholar 

  23. Vasdev SC, Kako KJ (1976) Metabolism of erucic acid in the isolated perfused rat heart. Biochim Biophys Acta 431:22–32

    PubMed  CAS  Google Scholar 

  24. Rønneberg R, Hølmer G, Lambertsen G (1986) Effects of feeding high-fat diets to rats: metabolism of erucic acid (C 22:1 n-9) in the perfused liver and secretion of metabolites to the perfusate. Ann Nutr Metab 30:345–356

    Article  PubMed  Google Scholar 

  25. Ward B, Harris P (1984) A comparison of the short-term incorporation of erucic acid and oleic acid in the perfused guinea-pig heart. J Mol Cell Cardiol. 16:897–903

    Article  PubMed  CAS  Google Scholar 

  26. Caselli C, Carlier H, Bezard J (1990) Erucic acid metabolism in rat heart. A combined biochemical and radioautographical study. Arch Int Physiol Biochim 98:377–395

    Article  PubMed  CAS  Google Scholar 

  27. Caselli C, Bernard A, Bezard J, Carlier H (1992) Erucic acid metabolism in rat liver: a combined biochemical and radioautographical study. Arch Int Physiol Biochim Biophys 100:309–320

    PubMed  CAS  Google Scholar 

  28. Ong N, Bezard J, Lecerf J (1977) Incorporation and metabolic conversion of erucic acid in various tissues of the rat in short term experiments. Lipids 12:563–569

    Article  PubMed  CAS  Google Scholar 

  29. Carroll KK (1962) Levels of radioactivity in tissues and in expired carbon dioxide after administration of 1-C14-labeled palmitic acid, 2-C14-labelled erucic acid, or 2-C14-labelled nervonic acid to rats. Can J Biochem Physiol 40:1229–1238

    PubMed  CAS  Google Scholar 

  30. Reubsaet FAG, Veerkamp JMF, Monnens LAH (1989) Total and peroxisomal oxidation of various saturated and unsaturated fatty acids in rat liver, heart and M quadriceps. Lipids 24:945–950

    Article  PubMed  CAS  Google Scholar 

  31. Clouet P, Bezard J (1978) Chain shortening of erucic acid by subcellular particles isolated from liver and heart of rat. FEBS Lett 93:165–168

    Article  PubMed  CAS  Google Scholar 

  32. Clouet P, Bezard J (1979) In vitro conversion of erucic acid by microsomes and mitochondria from liver, kidneys and heart of rats. Lipids 14:268–273

    Article  PubMed  CAS  Google Scholar 

  33. Christiansen EN, Thomassen MS, Christiansen RZ, Osmundsen H, Norum KR (1979) Metabolism of erucic acid in perfused rat liver: increased chain shortening after feeding partially hydrogenated marine oil and rapeseed oil. Lipids 14:829–835

    Article  PubMed  CAS  Google Scholar 

  34. Rønneberg R, Hølmer G, Lambertsen G (1987) Comparative metabolism of erucic and oleic acid in hepatocytes from rats fed partially hydrogenated marine oil or palm oil. Ann Nutr Metab 31:160–169

    PubMed  Google Scholar 

  35. Hølmer G, Rønneberg R (1986) Influence of dietary fat on metabolism of (14-14C)erucic acid in the perfused rat liver. Distribution of metabolites in lipid classes. Lipids 21:395–400

    Article  PubMed  Google Scholar 

  36. Neat CE, Thomassen MS, Osmundsen H (1980) Induction of peroxisomal β-oxidation in rat liver by high-fat diets. Biochem J 186:369–371

    PubMed  CAS  Google Scholar 

  37. Norseth J (1979) The effect of feed rats with partially hydrogenated marine oil or rapeseed oil on the chain shortening of erucic acid in perfused heart. Biochim Biophys Acta 575:1–9

    PubMed  CAS  Google Scholar 

  38. Hohl CM, Rosen P (1987) The role of arachidonic acid in rat heart cell metabolism. Biochim Biophys Acta 921:356–363

    PubMed  CAS  Google Scholar 

  39. Hagve T-A, Sprecher H (1989) Metabolism of long-chain polyunsaturated fatty acids in isolated cardiac myocytes. Biochim Biophys Acta 1001:338–344

    PubMed  CAS  Google Scholar 

  40. Saddik M, Lopaschuk GD (1991) The fate of arachidonic acid and linoleic acid in isolated working rat hearts containing normal or elevated levels of coenzyme A. Biochim Biophys Acta 1086:217–224

    PubMed  CAS  Google Scholar 

  41. Murphy EJ, Rosenberger TA, Patrick CB, Rapoport SI (2000) Intravenously injected [1-14C]arachidonic acid targets phospholipids, and [1-14C]palmitic acid targets neutral lipids in hearts of awake rats. Lipids 35:891–898

    Article  PubMed  CAS  Google Scholar 

  42. Robinson PJ, Noronha J, DeGeorge JJ, Freed LM, Nariai T, Rapoport SI (1992) A quantitative method for measuring regional in vivo fatty acid incorporation into and turnover within brain phospholipids: review and critical analysis. Brain Res Rev 17:187–214

    Article  PubMed  CAS  Google Scholar 

  43. Rapoport SI (1996) In vivo labeling of brain phospholipids by long-chain fatty acids: relation to turnover and function. Lipids 31:S97–S101

    Article  PubMed  CAS  Google Scholar 

  44. Rapoport SI, Chang MCJ, Spector AA (2001) Delivery and turnover of plasma-derived essential PUFAs in mammalian brain. J Lipid Res 42:678–685

    PubMed  CAS  Google Scholar 

  45. Rapoport SI (2005) In vivo approaches and rationale for quantifying kinetics and imaging brain lipid metabolic pathways. Prostaglandins Other Lipid Mediat 77:185–196

    Article  PubMed  CAS  Google Scholar 

  46. Golovko MY, Færgeman NJ, Cole NB, Castagnet PI, Nussbaum RL, Murphy EJ (2005) α-Synuclein gene-deletion decreases brain palmitate uptake and alters the palmitate metabolism in the absence of α-synuclein palmitate binding. Biochemistry 44:8251–8259

    Article  PubMed  CAS  Google Scholar 

  47. Golovko MY, Rosenberger TA, Færgeman NJ, Feddersen S, Cole NB, Pribill I, Berger J, Nussbaum RL, Murphy EJ (2006) Acyl-CoA synthetase activity links wild-type but not mutant α-synuclein to brain arachidonate metabolism. Biochemistry 45:6956–6966

    Article  PubMed  CAS  Google Scholar 

  48. Golovko MY, Rosenberger TA, Feddersen S, Færgeman NJ, Murphy EJ (2007) α-Synuclein gene ablation increases docosahexaenoic acid incorporation and turnover in brain phospholipids. J Neurochem 101:201–211

    Article  PubMed  CAS  Google Scholar 

  49. Freed LM, Wakabayashi S, Bell JM, Rapoport SI (1994) Effect of inhibition of β-oxidation on incorporation of [U-14C]palmitate and [1-14C]arachidonate into brain lipids. Brain Res 645:41–48

    Article  PubMed  CAS  Google Scholar 

  50. Folch J, Lees M, Sloan Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226:497–509

    PubMed  CAS  Google Scholar 

  51. Smith BSW (1970) A comparison of 125I and 51Cr for measurement of total blood volume and residual blood content of tissues in the rat; evidence for accumulation of 51Cr by tissues. Clinica Chimica Acta 27:105–108

    Article  CAS  Google Scholar 

  52. Regoeczi E, Taylor P (1978) The net weight of the rat liver. Growth 42:451–456

    PubMed  CAS  Google Scholar 

  53. Patrick CB, Rosenberger TA, McHowat J, Rapoport SI, Murphy EJ (2005) Arachidonic acid incorporation and turnover is decreased in sympathetically denervated rat heart. Am J Physiol 288:2611–2619

    Google Scholar 

  54. Radin NS (1988) Lipid extraction. In: Boulton AA, Baker GB, Horrocks LA (eds) Neuromethods 7 lipids and related compounds. Humana Press, Clifton, pp 1–62

    Google Scholar 

  55. Hara A, Radin NS (1978) Lipid extraction of tissues with a low-toxicity solvent. Anal Biochem 90:420–426

    Article  PubMed  CAS  Google Scholar 

  56. Saunders RD, Horrocks LA (1984) Simultaneous extraction and preparation for high-performance liquid chromatography of prostaglandins and phospholipids. Anal Biochem 143:71–75

    Article  PubMed  CAS  Google Scholar 

  57. Jolly CA, Hubbell T, Behnke WD, Schroeder F (1997) Fatty acid binding protein: stimulation of microsomal phosphatidic acid formation. Arch Biochem Biophys 341:112–121

    Article  PubMed  CAS  Google Scholar 

  58. Marcheselli VL, Scott BL, Reddy TS, Bazan NG (1988) Quantitative analysis of acyl group composition of brain phospholipids, neutral lipids, and free fatty acids. In: Boulton AA, Baker GB, Horrocks LA (eds) Neuromethods 7 lipids and related compounds. Humana Press, Clifton, pp 83–110

    Google Scholar 

  59. Murphy EJ, Schroeder F (1997) Sterol carrier protein-2 mediated cholesterol esterification in transfected L-cell fibroblasts. Biochim Biophys Acta 1345:283–292

    PubMed  CAS  Google Scholar 

  60. Jones M, Keenan RW, Horowitz P (1982) Use of 6-p-toluidino-2-naphthalenesulfonic acid to quantitate lipids after thin-layer chromatography. J Chromatogr 237:522–524

    Article  CAS  Google Scholar 

  61. Wood R, Lee T (1983) High-performance liquid chromatography of fatty acids: quantitative analysis of saturated, monoenoic, polyenoic and geometrical isomers. J Chromatogr 254:237–246

    Article  CAS  Google Scholar 

  62. Chen H, Anderson RE (1992) Quantitation of phenyl esters or retinal fatty acids by high-performance liquid chromatography. J Chromatogr 578:124–129

    Article  PubMed  CAS  Google Scholar 

  63. Miller JC, Gnaedinger JM, Rapoport SI (1987) Utilization of plasma fatty acid in rat brain: distribution of [14C]palmitate between oxidative and synthetic pathways. J Neurochem 49:1507–1514

    Article  PubMed  CAS  Google Scholar 

  64. Gnaedinger JM, Miller JC, Latker CH, Rapoport SI (1988) Cerebral metabolism of plasma 14Cpalmitate in awake adult rat: subcellular localization. Neurochem Res. 13:21–29

    Article  PubMed  CAS  Google Scholar 

  65. Berk PD, Stump DD (1999) Mechanisms of cellular uptake of long chain free fatty acids. Mol Cell Biochem 192:17–31

    Article  PubMed  CAS  Google Scholar 

  66. Norseth J, Christiansen EN, Christophersen BO (1979) Increased chain shortening of erucic acid in perfused heart from rats fed rapeseed oil. FEBS Lett 97:163–165

    Article  PubMed  CAS  Google Scholar 

  67. Rogers CG (1977) Erucic acid and phospholipids of newborn rat heart cells in culture. Lipids 12:375–381

    Article  PubMed  CAS  Google Scholar 

  68. Christiansen RZ, Christopherson BO, Bremer J (1977) Monoethylenic C20 and C22 fatty acids in marine oil and rapeseed oil. Studies on their oxidation and on their relative ability to inhibit palmitate oxidation in heart and liver mitochondria. Biochim Biophys Acta 487:28–36

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Carole Haselton for her excellent surgical and technical assistance and editorial suggestions and Mrs. Cindy Murphy for typing and preparation of the manuscript. This work was supported by grant from The Myelin Project to EJM and in part by a project (EJM) on a COBRE Grant from the National Institute of Health P20 RR17699.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Physiology, and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, 501 N. Columbia Rd, Grand Forks, ND, 58202-9037, USA

    Cameron C. Murphy, Eric J. Murphy & Mikhail Y. Golovko

  2. Department of Chemistry, University of North Dakota, Grand Forks, ND, 58202-9037, USA

    Eric J. Murphy

Authors
  1. Cameron C. Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eric J. Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mikhail Y. Golovko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eric J. Murphy.

About this article

Cite this article

Murphy, C.C., Murphy, E.J. & Golovko, M.Y. Erucic Acid is Differentially Taken up and Metabolized in Rat Liver and Heart. Lipids 43, 391–400 (2008). https://doi.org/10.1007/s11745-008-3168-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-008-3168-3

Keywords

Search

Navigation