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Why is carbon from some polyunsaturates extensively recycled into lipid synthesis?

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Lipids

Abstract

We summarize here the evidence indicating that carbon from α-linolenate and linoleate is readily recycled into newly synthesized lipids. This pathway consumes the majority of these fatty acids that is not β-oxidized as a fuel. Docosahexaenoate undergoes less β-oxidation and carbon recycling than do α-linolenate or linoleate, but is it still actively metabolized by this pathway? Among polyunsaturates, arachidonate appears to undergo the least β-oxidation and carbon recycling, an observation that may help account for the resistance of brain membranes to loss of arachidonate during dietary deficiency of n−6 polyunsaturates. Preliminary evidence suggests that de novo lipid synthesis consumes carbon from α-linolenate and linoleate in preference to palmitate, but this merits systematic study. Active β-oxidation and carbon recycling of 18-carbon polyunsaturates does not diminish the importance of being able to convert α-linolenate and linoleate to long-chain polyunsaturates but suggests that a broad perspective is required in studying the metabolism of polyunsaturates in general and α-linolenate and linoleate in particular.

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Abbreviations

ALA:

α-linolenate

DHA:

docosahexaenoate

HMG:

3-hydroxy-3-methylglutaryl

LA:

linoleate

LC-PUFA:

long-chain polyunsaturated fatty acids

References

  1. Cunnane, S.C., Menard, C.R., Likhodii, S.S., Brenna, J.T., and Crawford, M.A. (1999) Carbon Recycling into de novo Lipogenesis Is a Major Pathway in Neonatal Metabolism of Linoleate and α-Linolenate, Prostaglandins Leukot. Essent. Fatty Acids 60, 387–392.

    Article  CAS  PubMed  Google Scholar 

  2. Cunnane, S.C. (2001) New Developments in α-Linolenate Metabolism with Emphasis on the Importance of β-Oxidation and Carbon Recycling, World Rev. Nutr. Diet. 88, 178–183.

    CAS  PubMed  Google Scholar 

  3. Jones, P.J.H., and Schoeller, D.A. (1988) Polyunsaturated:Saturated Fatty Acid Ratio of Diet Fat Influences Energy Substrate Utilization in the Human Metabolism 37, 145–151.

    Article  CAS  PubMed  Google Scholar 

  4. Chen, Z.-Y., and Cunnane, S.C. (1993) Refeeding After Fasting Increases Apparent Oxidation of n−6 and n−3 Fatty Acids in Pregnant Rats, Metabolism 42, 1206–1211.

    Article  CAS  PubMed  Google Scholar 

  5. Cunnane, S.C., and Anderson, M.J. (1997) The Majority of Dietary Linoleate in Growing Rats Is β-Oxidized or Stored in Visceral Fat, J. Nutr. 127, 146–152.

    CAS  PubMed  Google Scholar 

  6. Poumes-Ballihaut, C., Langelier, B., Houlier, F., Alessandri, J.-M., Durand, G., Latge, C., and Guesnet, P. (2001) Comparative Bioavailability of Dietary α-Linolenic and Docosahexaenoic Acids in the Growing Rat, Lipids 36, 793–800.

    Article  CAS  PubMed  Google Scholar 

  7. Fu, Z., and Sinclair, A.J. (2000) Novel Pathway of Metabolism of α-Linolenic Acid in the Guinea Pig, Pediatr. Res. 47, 414–417.

    CAS  PubMed  Google Scholar 

  8. Fu, Z., Attar-Bashi, N.M., and Sinclair, A.J. (2001) I-14C-Linoleic Acid Distribution in Various Tissue Lipids of Guinea Pigs Following an Oral Dose, Lipids 36, 255–260.

    Article  CAS  PubMed  Google Scholar 

  9. Cunnane, S.C., Ross, R., Bannister, J.L., and Jenkins, D.J.A. (2001) β-Oxidation of Linoleate in Obese Men Undergoing Weight Loss, Am. J. Clin. Nutr. 73, 709–714.

    CAS  PubMed  Google Scholar 

  10. Leyton, J., Drury, P.J., and Crawford, M.A. (1987) Differential Oxidation of Saturated and Unsaturated Fatty Acids in vivo in the Rat, Br. J. Nutr. 57, 383–393.

    Article  CAS  PubMed  Google Scholar 

  11. Cunnane, S.C., and Yang, J. (1995) Zinc Deficiency Impairs Whole Body Accumulation of Polyunsaturates and Increase the Utilization of [1-14C]-Linoleate for de novo Lipid Synthesis in Pregnant Rats, Can. J. Physiol. Pharmacol. 73, 1246–1252.

    CAS  PubMed  Google Scholar 

  12. Sinclair, A.J. (1975) Incorporation of Radioactive Polyunsaturated Fatty Acids into Liver and Brain of the Developing Rat, Lipids 10, 175–184.

    Article  CAS  PubMed  Google Scholar 

  13. Dhopeswarkar, G.A., and Subramanian, C. (1975) Metabolism of α-Linolenic Acid in Developing Brain. I. Incorporation of Radioactivity from [1-14C]-α-Linolenic Acid into Brain Fatty Acids, Lipids 10, 238–241.

    Article  Google Scholar 

  14. Dhopeswarkar, G.A., and Subramanian, C. (1975) Metabolism of α-Linolenic Acid in Developing Brain. II. Incorporation of Radioactivity from [1-14C]-α-Linolenic Acid into Brain, Lipids 10, 242–247.

    Article  Google Scholar 

  15. Anderson, G.J., and Connor, W.E. (1988) Uptake of Fatty Acids by the Developing Brain, Lipids 23, 286–290.

    Article  CAS  PubMed  Google Scholar 

  16. Cunnane, S.C., Williams, S.C.R., Bell, J.D., Brookes, S., Craig, K., Iles, R.A., and Crawford, M.A. (1994) Utilization of [U-13C]-Labeled Polyunsaturated Fatty Acids in the Synthesis of Long-Chain Fatty Acids and Cholesterol Accumulating in Neonatal Rat Brain, J. Neurochem. 62, 2429–2436.

    Article  CAS  PubMed  Google Scholar 

  17. Sheaff-Greiner, R.C., Zhang, Q., Goodman, K.J., Guissini, D.A., Nathanielsz, P.W., and Brenna, J.T. (1996) Linoleate, α-Linolenate and Docosahexaenoate Recycling into Saturated and Monounsaturated Fatty Acids Is a Major Pathway in Pregnant or Lactating Adults and Fetal or Infant Rhesus Monkeys, J. Lipid Res. 37, 2675–2686.

    CAS  PubMed  Google Scholar 

  18. Edmond, J. (1974) Ketone Bodies as Precursors of Sterols and Fatty Acids in the Developing Rat, J. Biol. Chem. 249, 72–80.

    CAS  PubMed  Google Scholar 

  19. Emmison, N., Gallagher, P.A., and Coleman, R.A. (1995) Linoleic and α-Linolenic Acids Are Selectively Secreted in Triacylglycerol by Hepatocytes from Neonatal Rats, Am. J. Physiol. 269, R80-R86.

    CAS  PubMed  Google Scholar 

  20. Menard, C.R., Goodman, K.J., Corso, T.N., Brenna, J.T., and Cunnane, S.C. (1998) Recycling of Carbon into Lipids Synthesized de novo Is a Quantitatively Important Pathway of [U-13C]-α-Linolenate Utilization in the Developing Rat Brain, J. Neurochem. 71, 2151–2158.

    Article  CAS  PubMed  Google Scholar 

  21. Williard, D.E., Harmon, S.D., Kaduce, T.L., Preuss, M., Moore, S.A., Robbins, M.E.C., and Spector, A.A. (2001) Docosahexaenoic Acid Synthesis from n−3 Polyunsaturated Fatty Acids in Differentiated Rat Brain Astrocytes, J. Lipid Res. 42, 1368–1376.

    CAS  PubMed  Google Scholar 

  22. Cunnane, S.C., Belza, K., Anderson, M.J., and Ryan, M.A. (1998) Substantial Carbon Recycling from Linoleate into Products of de novo Lipogenesis Occurs in Rat Liver Even Under Conditions of Extreme Dietary Linoleate Deficiency, J. Lipid Res. 39, 2271–2276.

    CAS  PubMed  Google Scholar 

  23. Cunnane, S.C., Trotti, D., and Ryan, M.A. (2000) Specific Linoleate Deficiency in the Rat Does Not Prevent Substantial Carbon Recycling from [14C]-Linoleate into Sterols, J. Lipid Res. 41, 1808–1811.

    CAS  PubMed  Google Scholar 

  24. Wijendran, V., Lawrence, P., Diau, G.-Y., Boehm, G., Nathanielsz, P.W., and Brenna, J.T. (2002) Significant Utilization of Dietary Arachidonic Acid Is for Brain Adrenic Acid and Baboon Neonates, J. Lipid Res. 43, 762–767.

    CAS  PubMed  Google Scholar 

  25. Farquharson, J., Cockburn, F., Patrick, W.A., Jamieson, E.C., and Logan, R.W. (1992) Infant Cerebral Cortex Phospholipid Fatty Acid Composition and Diet, Lancet 340, 810–813.

    Article  CAS  PubMed  Google Scholar 

  26. Makrides, M., Neumann, M.A., Byard, R.W., Simmer, K., and Gibson, R.A. (1994) Fatty Acid Composition of Brain, Retina, and Erythrocytes in Breast- and Formula-Fed Infants, Am. J. Clin. Nutr. 60, 189–194.

    CAS  PubMed  Google Scholar 

  27. Moriguchi, T., Loewke, J., Garrison, M., Catalan, J.N., and Salem, N., Jr. (2001) Reversal of Docosahexaenoic Acid Deficiency in the Rat Brain, Retina, Liver and Serum, J. Lipid Res. 42, 419–427.

    CAS  PubMed  Google Scholar 

  28. Hahn, P., and Novak, M. (1985) How Important Are Carnitine and Ketones for the Newborn Infant? Fed. Proc. 44, 2369–2373.

    CAS  PubMed  Google Scholar 

  29. Vining, E.P.G. (1999) Clinical Efficacy of the Ketogenic Diet, Epilepsy Res. 37, 181–190.

    Article  CAS  PubMed  Google Scholar 

  30. Adam, P.A.J., Raiha, N., Rahiala, E.-L., and Kekomaki, M. (1975) Oxidation of Glucose and d-β-Hydroxybutyrate by the Early Fetal Human Brain, Acta Paediatr. Scand. 64, 17–24.

    Article  CAS  PubMed  Google Scholar 

  31. Bougneres, P.F., Lemmel, C., Ferre, P., and Bieur, D.M. (1986) Ketone Body Transport in the Human Neonate and Infant, J. Clin. Investig. 77, 42–48.

    Article  CAS  PubMed  Google Scholar 

  32. Kraus, H., Schlenker, S., and Schwedesky, D. (1974) Developmental Changes of Cerebral Ketone Body Utilization in Human Infants, Hoppe-Seyler's Z. Physiol. Chem. 355, 164–170.

    CAS  PubMed  Google Scholar 

  33. Webber, R.J., and Edmond, J. (1979) The in vivo Utilization of Acetoacetate, d(−)-3-Hydroxybutyrate and Glucose for Lipid Synthesis in the Brain of the 18 Day Old Rat: Evidence for an Acetyl CoA Bypass for Sterol Synthesis, J. Biol. Chem. 254, 3912–3920.

    CAS  PubMed  Google Scholar 

  34. Yeh, Y.-Y., Streuli, V.L., and Zee, P. (1977) Ketone Bodies Serve as Important Precursors of Brain Lipids in the Developing Rat, Lipids 12, 957–964.

    Article  CAS  PubMed  Google Scholar 

  35. Secombe, D.W., Harding, P.G.R., and Possmayer, F. (1977) Fetal Utilization of Maternally-Derived Ketone Bodies for Lipogenesis in the Rat, Biochim. Biophys. Acta 488, 402–416.

    Google Scholar 

  36. Devivo, D.C., Fishman, M.A., and Agrawal, H.C. (1973) Preferential Labeling of Brain Cholesterol by [3-14C] d(−)-3-Hydroxybutyrate, Lipids 8, 649–651.

    Article  CAS  PubMed  Google Scholar 

  37. Patel, M.S., Johnson, C.A., Rajan, R., and Owen, O.E. (1975) The Metabolism of Ketone Bodies in Developing Human Brain: Development of Ketone Body-Utilizing Enzymes and Ketone Bodies as Precursors for Lipid Synthesis, J. Neurochem. 25, 905–908.

    Article  CAS  PubMed  Google Scholar 

  38. Mauch, D., Nagler, K., Schumacher, S., Gorlitz, C., Muller, E.C., Otto, A., and Pfrieger, F.W. (2001) CNS Synaptogenesis Promoted by Glia-Derived Cholesterol, Science 294, 1354–1357.

    Article  CAS  PubMed  Google Scholar 

  39. Porter, J.A., Young, K.E., and Beachy, P.A. (1996) Cholesterol Modification of Hedgehog Signaling Proteins in Animal Development, Science 274, 255–259.

    Article  CAS  PubMed  Google Scholar 

  40. Jurevics, H., and Morell, P. (1995) Cholesterol for Synthesis of Myelin Is Made Locally, Not Imported into the Brain, J. Neurochem. 64, 895–901.

    Article  CAS  PubMed  Google Scholar 

  41. Zhang, S., Wong, W.W., Hachey, D.L., Pond, W.G., and Klein, P.D. (1994) Dietary Cholesterol Inhibits Whole-Body but Not Cerebrum Cholesterol Synthesis in Young Pigs, J. Nutr. 124, 717–725.

    CAS  PubMed  Google Scholar 

  42. Turley, S.D., Burns, D., Rosenfeld, C.R., and Dietschy, J.M. (1996) Brain Does Not utilize Low Density Lipoprotein-Cholesterol During Fetal and Neonatal Development in the Sheep, J. Lipid Res. 37, 1953–1961.

    CAS  PubMed  Google Scholar 

  43. Edmond, J., Higa, T.A., Korsak, R.A., Bergner, E.A., and Lee, W.N.P. (1998) Fatty Acid Transport and Utilization for the Developing Brain, J. Neurochem. 70, 1227–1234.

    Article  CAS  PubMed  Google Scholar 

  44. Poumes-Ballihaut, C. (2002) Effect of Dietary DHA on Membrane Lipids Composition of the Brain and Retina and on Two Neurophysiologic Functions in the Rat, Ph.D. Thesis, L'Ecole Nationale Superieure Agronomique de Rennes, Rennes, France.

    Google Scholar 

  45. Delaney, J.P., Windhauser, M.M., Champagne, C.M., and Bray, G.A. (2000) Differential Oxidation of Individual Dietary Fatty Acids in Humans, Am. J. Clin. Nutr. 72, 905–911.

    Google Scholar 

  46. Jones, P.J., Pencharz, P.B., and Clandinin, M.T. (1985) Whole Body Oxidation of Dietary Fatty Acids: Implications for Energy Utilization, Am. J. Clin. Nutr. 42, 769–777.

    CAS  PubMed  Google Scholar 

  47. McCloy, U. (2002) The Metabolism of Eighteen Carbon (13C) Unsaturated Fatty Acids in Healthy Women, Ph.D. Thesis, University of Toronto, Toronto, Canada.

    Google Scholar 

  48. Cenedella, R.J., and Allen, A. (1969) Differences Between the Metabolism of Linoleic and Palmitic Acid: Utilization for Cholesterol Synthesis and Oxidation to Respiratory CO2 Lipids 4, 155–158.

    Article  CAS  PubMed  Google Scholar 

  49. Dupont, J. (1966) Fatty Acid Oxidation in Relation to Cholesterol Biosynthesis in Rats Lipids 1, 415–421.

    Article  CAS  PubMed  Google Scholar 

  50. Clouet, P., Niot, I., and Bezard, J. (1989) Pathway of α-Linolenic Acid Through the Mitochondrial Outer Membrane in the Rat Liver and Influence on the Rate of Oxidation, Biochem. J. 263, 867–872.

    CAS  PubMed  Google Scholar 

  51. Gavino, G.R., and Gavino, V.C. (1991) Rat Liver Outer Mitochondrial Carnitine Palmitoyltransferase Activity Towards Long-Chain Polyunsaturated Fatty Acids and Their CoA Esters, Lipids 26, 266–270.

    Article  CAS  PubMed  Google Scholar 

  52. Bjorntorp, J. (1968) Rates of Oxidation of Different Fatty Acids by Isolated Rat Liver Mitochondria, J. Biol. Chem. 243, 2130–2133.

    CAS  PubMed  Google Scholar 

  53. Vasdev, S.C., and Kako, K.J. (1977) Incorporation of Fatty Acids into Rat Heart Lipids. In vivo and in vitro Studies, J. Mol. Cell. Cardiol. 9, 617–631.

    CAS  PubMed  Google Scholar 

  54. Anderson, G.J., and Connor, W.E. (1988) Uptake of Fatty Acids by the Developing Rat Brain, Lipids 23, 286–290.

    Article  CAS  PubMed  Google Scholar 

  55. Bandyopadhyay, G.K., Dutta, J., and Ghosh, S. (1982) Preferential Oxidation of Linolenic Acid Compared to Linoleic Acid in the Liver of Catfish (Heteropneustes fossilis and Clarias batrachus), Lipids 17, 733–740.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Stephen C. Cunnane.

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Cunnane, S.C., Ryan, M.A., Nadeau, C.R. et al. Why is carbon from some polyunsaturates extensively recycled into lipid synthesis?. Lipids 38, 477–484 (2003). https://doi.org/10.1007/s11745-003-1087-8

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  • DOI: https://doi.org/10.1007/s11745-003-1087-8

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