Abstract
Artificially reared infant rats were used to determine the effects of long-chain polyunsaturated fatty acid (LCP-UFA) supplementation on blood and tissue concentrations of arachidonic acid (AA) and docosahexaenoic acid (DHA). Beginning at 7 d of age, infant rats were fed for 10 d with rat milk formulas supplemented with AA at 0,0.5 and 1.0%, or supplemented with DHA at 0,0.5 and 1.0% of total fatty acid. The supplementation of AA increased accretion of the fatty acid in tissue and blood phospholipids with a maximum increase of 9% in brain, 15% in liver, 25% in erythrocytes, and 43% in plasma above the values of unsupplemented infant rats. Rat milk formula containing 1.0% of AA had no added benefits over that containing 0.5% of AA. The supplementation of DHA increased phospholipid DHA by a maximum of 24% in brain, 87% in liver, 54% in erythrocytes, and 360% in plasma above the unsupplemented control. The increase in tissue and blood DHA was concentration-dependent on formula fatty acid. Brain phosphatidylcholine and phosphatidylethanolamine were similarly enriched with AA and DHA by supplementation of the corresponding fatty acids. In general the observed increase of AA was accompanied by a decrease in 16:0, 18:1n−9, and/or 18:2n−6, whereas the increased DHA was associated with a reduction of 18:1n−9, 18:2n−6, and/or 20:4n−6. Clearly, infant rats were more responsive to DHA than AA supplementation, suggesting a great potential of dietary manipulation to alter tissue DHA concentrations. However, the supplementation of DHA significantly decreased tissue and blood AA/DHA ratios (wt%/wt%), whereas there was little or no change in the ratio by AA supplementation. Although the physiological implications of the levels of AA and DHA, and AA/DHA ratios achieved under the present experimental conditions are not readily known, the findings suggest that artificial rearing could provide a suitable model to investigate LCPUFA requirements using various sources of AA and DHA in rats.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Abbreviations
- AA:
-
arachidonic acid
- AR:
-
artificial rearing
- DHA:
-
docosahexaenoic acid
- EPA:
-
eicosapentaenoic acid
- LA:
-
linoleic acid
- I, N:
-
α-linolenic acid
- LCPUFA:
-
long-chain polyunsaturated fatty acids
- PC:
-
phosphatidylcholine
- PE:
-
phosphatidylethanolamine
- RMF:
-
rat milk formula
References
Breckenridge, W.C., Morgan, I.G., Zanetta, J.P., and Vincendon, G. (1973) Adult Rat Brain Synaptic Vesicles. II. Lipid Compositions, Biochim. Biophys. Acta 320, 681–686.
Connor, W.E., Neuringer, M., and Reisbick, S. (1992) Essential Fatty Acids: The Importance of n−3 Fatty Acids in the Retina and Brain, Nutr. Rev. 50, 21–29.
Martinez, M. (1992) Tissue Levels of Polyunsaturated Fatty Acids During Early Human Development, J. Pediatr. 120, S129-S138.
Leaf, A.A., Leighfield, M.J., Costeloe, K.L., and Crawford, M.A. (1992) Factors Affecting Long-Chain Polyunsaturated Fatty Acid Composition of Plasma Choline Phosphoglycerides in Preterm Infants, J. Pediatr. Gastroenterol. Nutr. 14, 300–308.
Foreman-van Drongelen, M.M., van Houwelingen, A.C., Kester, A.D., Hasaart, T.H., Blanco, C.E., and Hornstra, G. (1995) Long-Chain Polyunsaturated Fatty Acids in Preterm Infants: Status at Birth and Its Influence on Postnatal Levels, J. Pediatr. 126, 611–618.
Crawford, M.A. (1993) The Role of Essential Fatty Acids in Neural Development: Implications for Perinatal Nutrition, Am. J. Clin. Nutr. 57, 703S-710S.
Innis, S.M. (1993) Essential Fatty Acid Requirements in Human Nutrition, Can. J. Physiol. Pharmacol. 71, 699–706.
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.
Carlson, S.E., Werkman, S.H., and Tolley, E.A. (1996) Effect of Long-Chain n−3 Fatty Acid Supplementation on Visual Acuity and Growth of Preterm Infants With and Without Bronchopulmonary Dysplasia, Am. J. Clin. Nutr. 63, 687–697.
Agostoni, C., Trojan, S., Bellu, R., Riva, E., and Giovannini, M. (1995) Neurodevelopmental Quotient of Healthy Term Infants at 4 Months and Feeding Practice: The Role of Long-Chain Polyunsaturated Fatty Acids, Pediatr. Res. 38, 262–266.
Jorgensen, M.H., Hernell, O., Lund, P., Holmer, G. and Michaelsen, K.F. (1994) Visual Acuity and Erythrocyte Docosahexaenoic Acid Status in Breast-Fed and Formula-Fed Term Infants During the First Months of Life, Lipids 31, 99–105.
Makrides, M., Neumann, M., Simmer, K., Pater, J., and Gibson, R. (1995) Are Long-Chain Polyunsaturated Fatty Acids Essential Nutrients in Infancy? Lancet 345, 1463–1468.
Jensen, R.H., Hagerty, M.M., and McMahon, K.E. (1978) Lipids of Human Milk and Infant Formula: A Review, Am. J. Clin. Nutr. 31, 990–1016.
Sauerwald, T.U., Hachey, D.L., Jensen, C.L., Chen, H., Anderson, R.E., and Heird, W.C. (1996) Effect of Dietary α-Linolenic Acid Intake on Incorporation of Docosahexaenoic and Arachidonic Acids into Plasma Phospholipids of Term Infants, Lipids 31, S131-S135.
Putnam, J.C., Carlson, S.E., DeVoe, P.W., and Barness, L.A. (1982) The Effect of Variations in Dietary Fatty Acids on the Fatty Acid Composition of Erythrocyte Phosphatidylcholine and Phosphatidylethanolamine in Human Infants, Am. J. Clin. Nutr. 36, 106–114.
Carlson, S.E. (1996) Arachidonic Acid Status of Human Infants: Influence of Gestational Age at Birth and Diets with Very Long Chain n−3 and n−6 Fatty Acids, J. Nutr. 126, 1092S-1098S.
Decsi, T., Thiel, I., and Koletzko, B. (1995) Essential Fatty Acids in Full Term Infants Fed Breast Milk or Formula, Arch. Dis. Child. Fetal Neonat. Ed. 72, F23-F28.
Innis, S.M., Auestad, N., and Siegman, J.S. (1996) Blood Lipid Docosahexaenoic and Arachidonic Acid in Term Gestation Infants Fed Formulas with High Docosahexaenoic Acid, Low Eicosapentaenoic Acid Fish Oil, Lipids 31, 617–625.
Carlson, S.E., Ford, A.J., Werkman, S.H., Peeples, J.M., and Koo, W.W. (1996) Visual Acuity and Fatty Acid Status of Term Infants Fed Human Milk and Formulas With and Without Docosahexaenoate and Arachidonate from Egg Yolk Lecithin, Pediatr. Res. 39, 882–888.
Clark, K.J., Makrides, M., Neumann, M.A., and Gibson, R.A. (1992) Determination of the Optimal Ratio of Linoleic Acid to α-Linolenic Acid in Infant Formulas, J. Pediatr. 120, S151-S158.
Makrides, M., Neumann, M.A., Simmer, K., and Gibson, R.A. (1995) Erythrocyte Fatty Acids of Term Infants Fed Either Breast Milk, Standard Formula, or Formula Supplemented with Long-Chain Polyunsaturates, Lipids 30, 941–948.
Auestad, N., Montalto, M.B., Hall, R.T., Fitzgerald, K.M., Wheeler, R.E., Connor, W.E., Neuringer, M., Conner, S.L., Taylor, J.A., and Hartmann, E.E. (1997) Visual Acuity, Erythrocyte Fatty Acid Composition, and Growth in Term Infants Fed Formulas with Long Chain Polyunsaturated Fatty Acids for One Year. Ross Pediatric Lipid Study, Pediatr. Res. 41, 1–10.
Jensen, C.L., Chen, H., Fraley, J.K., Anderson, R.E., and Heird, W.C. (1996) Biochemical Effects of Dietary Linoleic-α-Linolenic Acid Ratio in Term Infants, Lipids 31, 107–113.
Innis, S.M., Nelson, C.M., Lwanga, D., Rioux, F.M. and Waslen, P. (1996) Feeding Formula Without Arachidonic Acid and Docosahexaenoic Acid Has No Effect on Preferential Looking Acuity or Recognition Memory in Healthy Full-Term Infants at 9 Mo of Age, Am. J. Clin. Nutr. 64, 40–46.
Innis, S.M., Akrabawi, S.S., Diersen-Schade, D.A., Dobson, M.V. and Guy, D.G. (1997) Visual Acuity and Blood Lipids in Term Infants Fed Human Milk or Formula, Lipids 32, 63–72.
Carlson, S.E., Werkman, S.H., Peeples, J.M., Cooke, R.J., and Tolley, E.A. (1993) Arachidonic Acid Status Correlates with First Year Growth in Preterm Infants, Proc. Natl. Acad. Sci. USA 90, 1073–1077.
Lands, W.E.M. (1991) Biosynthesis of Prostaglandins, Annu. Rev. Nutr. 11, 41–60.
Dobbing, J., and Sands, J. (1979) Comparative Aspects of Brain Growth Spurt, Early Hum. Dev. 3, 79–83.
Patel, M.S., and Hiremagalur, B.K. (1992) Artificial-Rearing Technique: Its Usefulness in Nutrition Research, J. Nutr. 122, 412–419.
Winters, B.L., Yeh, S.M., and Yeh, Y.Y. (1994) Linolenic Acid Provides a Source of Docosahexaenoic Acid for Artificially Reared Rat Pups, J. Nutr. 124, 1654–1659.
Ward, G., Woods, J., Reyzer, M., and Salem, N., Jr. (1996) Artificial Rearing of Infant Rats on Milk Formula Deficient in n−3 Essential Fatty Acids: A Rapid Method for the Production of Experimental n−3 Deficiency, Lipids 31, 71–77.
Hall, W.G. (1975) Weaning and Growth of Artificially Reared Rats, Science 190, 1313–1315.
Auestad, N., Korsak, R.A., Bergstrom, J.D., and Edmond, J. (1989) Milk-Substitutes Comparable to Rat's Milk: Their Preparation, Composition and Impact on Development and Metabolism in the Artificially Reared Rat, Br. J. Nutr. 61, 495–518.
Yeh, Y.Y., Winters, B.L., and Yeh, S.M. (1990) Enrichment of (n−3) Fatty Acids of Suckling Rats by Maternal Dietary Menhaden Oil, J. Nutr. 120, 436–443.
Folch, J., Lee, M., and Sloane-Stanley, G.H. (1957) A Simple Method for the Isolation and Purification of Total Lipids from Animal Tissues, J. Biol. Chem. 226, 497–510.
Yeh, Y.Y., Streuli, V.L., and Zee, P. (1977) Relative Utilization of Fatty Acids for Synthesis of Ketone Bodies and Complex Lipids in the Liver of Developing Rats, Lipids 12, 367–374.
Morrison, W.R. and Smith, L.M. (1964) Preparation of Fatty Acid Methyl Esters and Dimethylacetals from Lipid from Boron Fluoride Methanol, J. Lipid Res. 5, 600–608.
Pai, T.K., and Yeh, Y.Y. (1997) Desaturation of Sterate Is Insufficient to Increase the Concentrations of Oleate in Cultured Rat Hepatocytes, J. Nutr. 127, 753–757.
Yeh, Y.Y., Gehman, M.F., and Yeh, S.M. (1993) Maternal Dietary Fish Oil Enriches Docosahexaenoate Levels in Brain Subcellular Fractions of Offspring, J. Neurosci. Res. 35, 218–226.
Milton, J.S. (1992) Statistical Methods in the Biological and Health Sciences, 2nd edn., pp. 303–306, McGraw-Hill, Inc., New York.
Innis, S.M. (1992) Plasma and Red Blood Cell Fatty Acid Values as Indexes of Essential Fatty Acids in the Developing Organs of Infants Fed with Milk or Formulas, J. Pediatr. 120, S78-S86.
Van Aerde, J.E., and Clandinin, M.T. (1993) Controversy in Fatty Acid Balance, Can. J. Physiol. Pharmacol. 71, 707–712.
Salem, N., Jr., Wegher, B., Mena, P., and Uauy, R. (1996) Arachidonic and Docosahexaenoic Acids Are Biosynthesized from Their 18-Carbon Precursors in Human Infants, Proc. Natl. Acad. Sci. USA 93, 49–54.
Carlson, S.E., and Werkman, S.H. (1996) A Randomized Trial of Visual Attention of Preterm Infants Fed Docosahexaenoic Acid Until Two Months, Lipids 31, 85–90.
Werkman, S.H., and Carlson, S.E. (1996) A Randomized Trial of Visual Attention of Preterm Infants Fed Docosahexaenoic Acid Until Nine Months, Lipids 31, 91–97.
Makrides, M., Simmers, K., Goggin, M., and Gibson, R.A. (1993) Erythrocyte Docosahexaenoic Acid Correlated With the Visual Response of Healthy Term Infants, Pediatr. Res. 34, 425–427.
Rioux, F.M., and Innis, S.M. (1992) Arachidonic Acid Concentrations in Plasma and Liver Phospholipid and Cholesterol Esters of Piglets Raised on Formulas with Different Linoleic and Linolenic Acid Contents., Am. J. Clin. Nutr. 56, 106–112.
Innis, S.M., Roux, F.M., Auestad, N., and Ackman, R.G. (1995) Marine and Freshwater Fish Oils Varying in Arachidonic, Eicosapentaenoic and Docosahexaenoic Acids Differ in Their Effects on Organ Lipids and Fatty Acids in Growing Rats, J. Nutr. 125, 2286–2293.
Craig-Schmidt, M.C., Stieh, K.E., and Lien, E.L. (1996) Retinal Fatty Acids of Piglets Fed Docosahexaenoic and Arachidonic Acids from Microbial Sources, Lipids 31, 53–59.
Nilsson, A., Hjelte, L., and Strandvik, B. (1996) Metabolism of Orally Fed [3H]-Eicosapentaenoic Acid and [14C]-Arachidonic Acid in Essential Fatty Acid-Deficient Rats, Scand. J. Clin. Lab. Invest. 56, 219–227.
Liu, C.-C.F., Carlson, S.E., Rodes, P.G., Rao, V.S., and Meydreck, E.F. (1987) Increase in Plasma Phospholipid Docosahexaenoic Acid and Eicosapentaenoic Acid as a Reflection of Their Intake and Mode of Administration, Pediatr. Res. 22, 292–296.
Uauy, R.D., Birch, D.G., Tyson, J.E., and Hoffman, D.R. (1990) Effect of Dietary Omega-3 Fatty Acids on Retinal Function of Very-Low-Birth-Weight Neonates, Pediatr. Res. 28, 485–492.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Yeh, YY., Yeh, SM. & Lien, E.L. Modification of milk formula to enhance accretion of long-chain n−6 and n−3 polyunsaturated fatty acids in artificially reared infant rats. Lipids 33, 513–520 (1998). https://doi.org/10.1007/s11745-998-0235-5
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11745-998-0235-5