Abstract
Fish oil-enriched diets increase n−3 FA in tissue phospholipids; however, a similar effect by plant-derived n−3 FA is poorly defined. To address this question, we determined mass changes in phospholipid FA, individual phospholipid classes, and cholesterol in the liver, heart, and brain of rats fed diets enriched in flax oil (rich in 18∶3n−3), fish oil (rich in 22∶6n−3 and 20∶5n−3), or safflower oil (rich in 18∶2n−6) for 8 wk. In the heart and liver phospholipids, 22∶6n−3 levels increased only in the fish oil group, although rats fed flax oil accumulated 20∶5n−3 and 22∶5n−3. However, in the brain, the flax and fish oil diets increased the phospholipid 22∶6n−3 mass. In all tissues, these diets decreased the 20∶4n−6 mass, although the effect was more marked in the fish oil than in the flax oil group. Although these data do not provide direct evidence for 18∶3n−3 elongation and desaturation by the brain, they demonstrate that 18∶3n−3-enriched diets reduced tissue 20∶4n−6 levels and increased cellular n−3 levels in a tissuedependent manner. We hypothesize, based on the lack of increased 22∶6n−3 but increased 18∶3n−3 in the liver and heart, that the flax oil diet increased circulating 18∶3n−3, thereby presenting tissue with this EFA for further elongation and desaturation.
Similar content being viewed by others
Abbreviations
- 18∶1n−9:
-
oleic acid
- 18∶2n−6:
-
linoleic acid
- 18∶3n−3:
-
α-linolenic acid
- 20∶3n−9:
-
Mead acid
- 20∶4n−6:
-
arachidonic acid
- 20∶5n−3:
-
eicosapentaenoic acid
- 22∶5n−3:
-
docosapentaenoic acid
- 22∶5n−6:
-
docosapentaenoic acid n−6
- 22∶6n−3:
-
docosahexaenoic acid
- CerPCho:
-
sphingomyelin
- ChoGpl:
-
choline glycerophospholipids
- EtnGpl:
-
ethanolamine glycerophospholipids
- PlsCho:
-
1-O-alkyl-1′-enyl-2-acyl-sn-glycero-3-phosphocholine
- PlsEtn:
-
1-O-alkyl-1′-enyl-2-acyl-sn-glycero-3-phosphoethanolamine
- Ptd2Gro:
-
cardiolipin
- PtdIns:
-
phosphatidylinositol
- PtdOH:
-
phosphatidic acid
- PtdSer:
-
phosphatidylserine
References
Lauritzen, L., Hansen, H.S., Jørgensen, M.H., and Michaelsen, K.F. (2001) The Essentiality of Long-Chain n−3 Fatty Acids in Relation to Development and Function of the Brain and Retina, Prog. Lipid Res. 40, 1–94.
Leaf, A., Kang, J.X., Xiao, Y.-F., and Billman, G.E. (2003) Clinical Prevention of Sudden Cardíac Death by n−3 Polyunsaturated Fatty Acids and Mechanism of Prevention of Arrhythmias by n−3 Fish Oils, Circulation 107, 2646–2652.
Stoll, A.L., Severus, W.E., Freeman, M.P., Rueters, S., Zboyan, H.A., Diamond, E., Cress, K.K., and Marangell, L.B. (1999) Omega 3 Fatty Acids in Bipolar Disorder: A Preliminary Double-Blind, Placebo-Controlled Trial, Arch. Gen. Psychiatry 56, 407–412.
Wijendran, V., and Hayes, K.C. (2004) Dietary n−6 and n−3 Fatty Acid Balance and Cardiovascular Health, Annu. Rev. Nutr. 24, 597–615.
Sunshine, C., and McNamee, M.G. (1994) Lipid Modulation of Nicotinic Acetylcholine Receptor Function: The Role of Membrane Lipid Composition and Fluidity, Biochim. Biophys. Acta 1191, 59–64.
Gerbi, A., Maixent, J.-M., Barbey, O., Jamme, I., Pierlovisi, M., Coste, T., Pieroni, G., Novelot, A., Vague, P., and Raccah, D. (1998) Alterations of Na,K-ATPase Isoenzymes in the Rat Diabetic Neuropathy: Protective Effect of Dietary Supplementation with n−3 Fatty Acids, J. Neurochem. 71, 732–740.
Cannon, B., Hermansson, M., Györke, S., Somerharju, P., Virtanen, J.A., and Cheng, K.H. (2003) Regulation of Calcium Channel Activity by Lipid Domain Formation in Planar Lipid Bilayers, Biophys. J. 85, 933–942.
Lesa, G.M., Palfreyman, M., Hall, D.H., Clandinin, M.T., Rudolph, C., Jorgensen, E.M., and Schiavo, G. (2003) Long Chain Polyunsaturated Fatty Acids Are Required for Efficient Neurotransmission in C. elegans, J. Cell Sci. 116, 4965–4975.
Kodas, E., Galineau, L., Bodard, S., Vancassel, S., Guilloteau, D., Besnard, J.-C., and Chalon, S. (2004) Sertoninergic Neurotransmission Is Affected by n−3 Polyunsaturated Fatty Acids in the Rat, J. Neurochem. 89, 695–702.
Pepe, S., and McLennan, P.L. (2002) Cardiac Membrane Fatty Acid Composition Modulates Myocardial Oxygen Consumption and Postischemic Recovery of Contractile Function, Circulation, 105, 2303–2308.
Gilroy, D.W., Newson, J., Sawmynaden, P., Willoughby, D.A., and Croxtall, J.D. (2004) A Novel Role for Phospholipase A2 Isoforms in the Checkpoint Control of Acute Inflammation, FASEB J. 18, 489–498.
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.
Poumès-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.
Bowen, R.A.R., and Clandinin, M.T. (2000) High Dietary 18∶3n−3 Increases in the 18∶3n−3 but Not the 22∶6n−3 Content in the Whole Body, Brain, Skin, Epididymal Fat Pads, and Muscles of Suckling Rat Pups, Lipids 35, 389–394.
MacDonald-Wicks, L.K., and Garg, M.L. (2004) Incorporation of n−3 Fatty Acids into Plasma and Liver Lipids of Rats: Importance of Background Dietary Fat, Lipids 39, 545–551.
Morise, A., Combe, N., Boué, C., Legrand, P., Catheline, D., Delplanque, B., Fénart, E., Weill, P., and Hermier, D. (2004) Dose Effect of α-Linolenic Acid on PUFA Conversion, Bioavailability, and Storage in the Hamster, Lipids 39, 325–334.
Abedin, L., Lien, E.L., Vingrys, A.J., and Sinclair, A.J. (1999) The Effects of Dietary α-Linolenic Acid Compared with Docosahexaenoic Acid on Brain, Retina, Liver, and Heart in the Guinea Pig, Lipids 34, 475–482.
Bazinet, R.P., McMillan, E.G., and Cunnane, S.C. (2003) Dietary α-Linolenic Acid Increases the n−3 PUFA Content of Sow’s Milk and the Tissues of the Suckling Piglet, Lipids 38, 1045–1049.
Su, H.M., Huang, M.C., Saad, N.M., Nathanielsz, P.W., and Brenna, J.T. (2001) Fetal Baboons Convert 18∶3n−3 to 22∶6n−3 in vivo. A Stable Isotope Tracer Study, J. Lipid Res. 42, 581–586.
Mantzioris, E., James, M.J., Gibson, R.A., and Cleland, L.G. (1994) Dietary Substitution with an α-Linolenic Acid-rich Vegetable Oil Increases Eicosapentaenoic Acid Concentrations in Tissues, Am. J. Clin. Nutr. 59, 1304–1309.
Burdge, G.C., Jones, A.E., and Wooton, S.A. (2002) Eicosapentaenoic and Docosapentaenoic Acids Are the Principal Products of α-Linolenic Acid Metabolism in Young Men, Br. J. Nutr. 88, 355–363.
Burdge, G. (2004) α-Linolenic Acid Metabolism in Men and Women: Nutritional and Biological Implications, Curr. Opin. Clin. Nutr. Metab. Care 7, 137–144.
Barcelo-Coblijn, G., Kitajka, K., Puskas, L.G., Hogyes, E., Zvara, A., Hackler, L., Jr., and Farkas, T. (2003) Gene Expression and Molecular Composition of Phospholipids in Rat Brain in Relation to Dietary n−6 and n−3 Fatty Acid Ratio, Biochim. Biophys. Acta 1632, 72–79.
Meyer, B.J., Mann, N.J., Lewis, J.L., Milligan, G.C., Sinclair, A.J., and Howe, P.R. (2003) Dietary Intakes and Food Sources of Omega-6 and Omega-3 Polyunsaturated Fatty Acids, Lipids 38, 391–398.
Astorg, P., Arnault, N., Czernichow, S., Noisette, N., Galan, P., and Hercberg, S. (2004) Dietary Intakes and Food Sources of n−6 and n−3 PUFA in French Adult Men and Women, Lipids 39, 527–535.
Reeves, P.G., Nielsen, F.H., and Fahey, C.G., Jr. (1993) AIN-93 Purified Diets for Laboratory Rodents: Final Report of the American Institute of Nutrition ad hoc Writing Committee on the Reformation of the AIN-76A Rodent Diet, J. Nutr. 123 1939–1951.
Hara, A., and Radin, N.S. (1978) Lipid Extraction of Tissues with a Low-Toxicity Solvent, Anal. Biochem. 90, 420–426.
Radin, N.S. (1988) Lipid Extraction, in Neuromethods, Vol. 7, Lipids and Related Compounds (Boulton, A.A., Baker, G.B., and Horrocks, L.A., eds.), pp. 1–61, Humana Press, Clifton, NJ.
Jolly, C.A., Hubbell, T., Behnke, W.D., and Schroeder, F. (1997) Fatty Acid Binding Protein: Stimulation of Microsomal Phosphatidic Acid Formation, Arch. Biochem. Biophys. 341, 112–121.
Marcheselli, V.L., Scott, B.L., Reddy, T.S., and Bazan, N.G. (1988) Quantitative Analysis of Acyl Group Composition of Brain Phospholipids, Neutral Lipids, and Free Fatty Acids, in Neuromethods, Vol. 7, Lipids and Related Compounds (Boulton, A.A., Baker, G.B., and Horrocks, L.A., eds.), pp. 83–110, Humana Press, Clifton, NJ.
Dugan, L.L., Demediuk, P., Pendley, C.E., II, and Horrocks, L.A. (1986) Separation of Phospholipids by High Pressure Liquid Chromatography: All Major Classes Including Ethanolamine and Choline Plasmalogens, and Most Minor Classes, Including Lysophosphatidylethanolamine, J. Chromatogr. 378, 317–327.
Murphy, E.J., Stephens, R., Jurkowitz-Alexander, M., and Horrocks, L.A. (1993) Acidic Hydrolysis of Plasmalogens Followed by High-Performance Liquid Chromatography, Lipids 28, 565–568.
Rouser, G., Siakotos, A., and Fleischer, S. (1969) Quantitative Analysis of Phospholipids by Thin Layer Chromatography and Phosphorus Analysis of Spots, Lipids 1, 85–86.
Bowman, R.E., and Wolf, R.C. (1962) A Rapid and Specific Ultramicro Method for Total Serum Cholesterol, Clin. Chem. 8, 302–309.
Brockerhoff, H. (1975) Determination of the Positional Distribution of Fatty Acids in Glycerolipids, Methods Enzymol. 35, 315–325.
Gross, R.W. (1985) Identification of Plasmalogen as the Major Phospholipid Constituent of Cardiac Sarcoplasmic Reticulum, Biochemistry 24, 1662–1668.
Gross, R.W. (1984) High Plasmalogen and Arachidonic Acid Content of Canine Myocardial Sarcolemma: A Fast Atom Bombardment Mass Spectroscopic and Gas Chromatography-Mass Spectroscopic Characterization, Biochemistry 23, 158–165.
Horrocks, L.A. (1967) Composition of Myelin from Peripheral and Central Nervous System of the Squirrel Monkey, J. Lipid Res. 8, 569–576.
Horrocks, L.A., and Sun, G.Y. (1972) Ethanolamine Plasmalogens, in Research Methods in Neurochemistry, Vol. 1 (Rodnight, R., and Marks, N., eds.), pp. 223–231, Plenum Press, New York.
Lin, D.S., Connor, W.E., Anderson, G.J., and Neuringer, M. (1990) Effects of Dietary n−3 Fatty Acids on the Phospholipid Molecular Species of Monkey Brain, J. Neurochem. 55 1200–1207.
Heemskerk, J.W., Feijge, M.A., Simonis, M.A., and Hornstra, G. (1995) Effects of Dietary Fatty Acids on Signal Transduction and Membrane Cholesterol Content in Rat Platelets, Biochim. Biophys. Acta 1255, 87–97.
Greiner, R.S., Catalan, J.N., Moriguchi, T., and Salem, N., Jr. (2003) Docosapentaenoic Acid Does Not Completely Replace DHA in n−3 FA-Deficient Rats During Early Development, Lipids 38, 431–435.
Bourre, J.M., Dumont, O., Pascal, G., and Durand, G. (1993) Dietary α-Linolenic Acid at 1.3 g/kg Maintains Maximal Docosahexaenoic Acid Concentration in Brain, Heart and Liver of Adult Rats, J. Nutr. 123, 1313–1319.
Stubbs, C.D., and Smith, A.D. (1984) The Modification of Mammalian Membrane Polyunsaturated Fatty Acid Composition in Relation to Membrane Fluidity and Function, Biochim. Biophys. Acta 779, 89–137.
Clamp, A.G., Ladha, S., Clark, D.C., Grimble, R.F., and Lund, E.K. (1997) The Influence of Dietary Lipids on the Composition and Membrane Fluidity of Rat Hepatocyte Plasma Membrane, Lipids 32, 179–184.
Jump, D.B. (2002) The Biochemistry of n−3 Polyunsaturated Fatty Acids, J. Biol. Chem. 277, 8755–8758.
Marcheselli, V.L., Hong, S., Lukiw, W.J., Tian, X.H., Gronert, K., Musto, A., Hardy, M., Giminez, J.M., Chiang, N., Serhan, C.N., et al. (2003) Novel Docosanoids Inhibit Brain Ischemia-Reperfusion-Mediated Leukocyte Infiltration and Pro-inflammatory Gene Expression, J. Biol. Chem. 278, 43807–43817.
Zhao, G., Etherton, T.D., Martin, K.R., West, S.G., Gillies, P.J., and Kris-Etherton, P.M. (2004) Dietary α-Linolenic Acid Reduces Inflammatory and Lipid Cardiovascular Risk Factors in Hypercholesterolemic Men and Women, J. Nutr. 134, 2991–2997.
Bemelmans, W.J.E., Broer, J., Feskens, E.J.M., Smit, A.J., Muskiet, F.A.J., Lefrandt, J.D., Bom, V.J.J., May, J.F., and Meyboom-de Jong, B. (2002) Effect of an Increased Intake of α-Linolenic Acid and Group Nutritional Education on Cardiovascular Risk Factors: The Mediterranean α-Linolenic Enriched Groningen Dietary Intervention (MARGARIN) Study, Am. J. Clin. Nutr. 75, 221–227.
Djoussé, L., Pankow, J.S., Eckfeldt, J.H., Folsom, A.R., Hopkins, P.N., Province, M.A., Hong, Y., and Ellison, R.C. (2001) Relation Between Dietary Linolenic Acid and Coronary Artery Disease in the National Heart, Lung, and Blood Institute Family Heart Study, Am. J. Clin. Nutr. 74, 612–619.
de Groot, R.H.M., Hornstra, G., van Houwelingen, A.C., and Roumen, F. (2004) Effect of α-Linolenic Acid Supplementation During Pregnancy on Maternal and Neonatal Polyunsaturated Fatty Acid Status and Pregnancy Outcome, Am. J. Clin. Nutr. 79, 251–260.
Pawlosky, R.J., Hibbeln, J.R., Novotny, J.A., and Salem, N., Jr. (2001) Physiological Compartmental Analysis of α-Linolenic Acid Metabolism in Adult Humans, J. Lipid Res. 42, 1257–1265.
Pawlosky, R.J., Ward, G., and Salem, N., Jr. (1996) Essential Fatty acid Uptake and Metabolism in the Developing Rodent Brain, Lipids 31, S103-S107.
Dhopeshwarkar, G.A., and Subramanian, C. (1976) Biosynthesis of Polyunsaturated Fatty Acids in the Developing Brain: I. Metabolic Transformations of Intracranially Administered 1–14C Linolenic Acid, Lipids 11, 67–71.
Cho, H.P., Nakamura, M., and Clarke, S.D. (1999) Cloning, Expression, and Fatty Acid Regulation of the Human Δ-5 Desaturase, J. Biol. Chem. 274, 37335–37339.
Cho, H.P., Nakamura, M.T., and Clarke, S.D. (1999) Cloning, Expression, and Nutritional Regulation of the Mammalian Δ-6 Desaturase, J. Biol. Chem. 274, 471–477.
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.
Bernoud, N., Fenart, L., Bénistant, C., Pageaux, J.F., Dehouck, M.P., Molière, P., Lagarde, M., Cecchelli, R., and Lecerf, J. (1998) Astrocytes Are Mainly Responsible for the Polyunsaturated Fatty Acid Enrichment in Blood-Brain Barrier Endothelial Cells in vitro, J. Lipid Res. 39, 1816–1824.
Mohrmauer, H., Christiansen, K., Gan, M.V., Deubig, M., and Holman, R.T. (1967) Chain Elongation of Linoleic Acid and Its Inhibition by Other Fatty Acids in vitro, J. Biol. Chem. 242, 4507–4514.
Watson, A.D., Leitinger, N., Navab, M., Faull, K.F., Hörkkö, S., Witztum, J.L., Palinski, W., Schwenke, D., Salomon, R.G., Sha, W., et al. (1997) Structural Identification by Mass Spectrometry of Oxidized Phospholipids in Minimally Oxidized Low Density Lipoprotein That Induce Monocyte/Endothelial Interactions and Evidence for Their Presence in vivo, J. Biol. Chem. 272, 13597–13607.
Calder, P.C. (2001) Polyunsaturated Fatty Acids, Inflammation, and Immunity, Lipids 36, 1007–1024.
Rosenberger, T.A., Villacreses, N.E., Hovda, J.T., Boestti, F., Weerasinghe, G., Wine, R.N., Harry, G.J., and Rapoport, S.I. (2004) Rat Brain Arachidonic Acid Metabolism Is Increased by a 6-Day Intracerebral Ventricular Infusion of Bacterial Lipopolysaccharide, J. Neutrochem. 88, 1168–1178.
Lee, H., Villacreses, N.E., Rapoport, S.I., and Rosenberger, T.A. (2004) In vivo Imaging Detects a Transient Increase in Brain Arachidonic Acid Metabolism: A Potential Marker of Neuroinflammation, J. Neurochem. 91, 936–945.
Avis, I., Hong, S.H., Martinez, A., Moody, T., Choi, Y.H., Trepel, J., Das, R., Jett, M., and Mulshine, J.L. (2001) Five-Lipoxygenase Inhibitors Can Mediate Apoptosis in Human breast Cancer Cell Lines Through Complex Eicosanoid Interactions, FASEB J. 15, 2007–2009.
Khuu Thi-Dinh, K.L., Demarne, Y., Nicolas, C., and Lhuillery, C. (1990) Effect of Dietary Fat on Phospholipid Class Distribution and Fatty Acid Composition in Rat Fat Cell Plasma Membrane, Lipids 25, 278–283.
Turini, M.E., Thomson, A.B., and Clandinin, M.T. (1991) Lipid Composition and Peroxide Levels of Mucosal Cells in the Rat Large Intestine in Relation to Dietary Fat, Lipids 26, 431–440.
Gibson, R.A., Neumann, M.A., Burnard, S.L., Rinaldi, J.A., Patten, G.S., and McMurchie, E.J. (1992) The Effect of Dietary Supplementation with Eicosapentaenoic Acid on the Phospholipid and Fatty Acid Composition of Erythrocytes of Marmoset, Lipids 27, 169–176.
Oliveros, L.B., Videla, A.M., Ramirez, D.C., and Gimenez, M.S. (2003) Dietary Fat Saturation Produces Lipid Modifications in Peritoneal Macrophages of Mouse, J. Nutr. Biochem. 14, 370–377.
Jefferson, J.R., Powell, D.M., Rymaszewski, Z., Kukowska-Latallo, J., Lowe, J.B., and Schroeder, F. (1990) Altered Membrane Structure in Transfected Mouse L-Cell Fibroblasts Expressing Rat Liver Fatty Acid Binding Protein, J. Biol. Chem. 265, 11062–11068.
Woodford, J.K., Jefferson, J.R., Wood, W.G., Hubbell, T., and Schroeder, F. (1993) Expression of Liver Fatty Acid Binding Protein Alters Membrane Lipid Composition and Structure in Transfected L-Cell Fibroblasts, Biochim. Biophys. Acta 1145, 257–265.
Murphy, E.J., Prows, D., Stiles, T., and Schroeder, F. (2000) Phospholipid and Phospholipid Fatty Acid Composition of L-Cell Fibroblast: Effect of Intestinal and Liver Fatty Acid Binding Protein, Lipids 35, 729–738.
Arbuckle, L.D., and Innis, S.M. (1992) Docosahexaenoic Acid in Developing Brain and Retina of Piglets Fed High or Low α-Linolenate Formula With and Without Fish Oil, Lipids 27, 89–93.
Valenzuela, A., von Bernhardi, R., Valenzuela, V., Ramírez, G., Alarcón, R., Sanjueza, J., and Nieto, S. (2004) Supplementation of Female Rats with α-Linolenic Acid or Docosahexaenoic Acid Leads to the Same Omega-6/Omega-3 LC-PUFA Accretion in Mother Tissues and in Fetal and Newborn Brains, Ann. Nutr. Metab. 48, 28–35.
Lefkowitz, W., Lim, S.-Y., Lin, Y., and Salem, N., Jr. (2005) Where Does the Developing Brain Obtain Its Docosahexaenoic Acid? Relative Contributions of Dietary α-Linolenic Acid, Docosahexaenoic Acid, and Body Stores in the Developing Rat, Pediatr. Res. 57, 157–165.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Barceló-Coblijn, G., Collison, L.W., Jolly, C.A. et al. Dietary α-linolenic acid increases brain but not heart and liver docosahexaenoic acid levels. Lipids 40, 787–798 (2005). https://doi.org/10.1007/s11745-005-1440-y
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11745-005-1440-y