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Essential fatty acids in early life: structural and functional role

Published online by Cambridge University Press:  28 February 2007

Ricardo Uauy ,
Patricia Mena  and
Cecilia Rojas
Ricardo Uauy*
Affiliation:
Institute of Nutrition and Food Technology (INTA), University of Chile, Macul 5540, Casilla 138-11, Santiago, Chile Retina Foundation of the Southwest, Dallas, TX, USA
Patricia Mena
Affiliation:
Institute of Nutrition and Food Technology (INTA), University of Chile, Macul 5540, Casilla 138-11, Santiago, Chile
Cecilia Rojas
Affiliation:
Institute of Nutrition and Food Technology (INTA), University of Chile, Macul 5540, Casilla 138-11, Santiago, Chile
*
*Corresponding author: Dr R. Uauy, fax +56 2 221 4030, email uauy@abello.dic.uchile.cl
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Abstract

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Essential fatty acids (EFA) are structural components of all tissues and are indispensable for cell membrane synthesis; the brain, retina and other neural tissues are particularly rich in long-chain polyunsaturated fatty acids (LCPUFA). These fatty acids serve as specific precursors for eicosanoids that regulate numerous cell and organ functions. Results from animal and recent human studies support the essential nature of n-3 EFA in addition to the well-established role of n-6 EFA for human subjects, particularly in early life. The most significant effects relate to neural development and maturation of sensory systems. Recent studies using stable-isotope-labelled tracers demonstrate that even preterm infants are able to form arachidonic acid (AA) and docosahexaenoic acid (DHA), but that synthesis is extremely low. Intracellular fatty acids or their metabolites regulate transcriptional activation of gene expression during adipocyte differentiation, and retinal and nervous system development. Regulation of gene expression by LCPUFA occurs at the transcriptional level and is mediated by nuclear transcription factors activated by fatty acids. These nuclear receptors are part of the steroid hormone receptor family. Two types of polyunsaturated fatty acid responsive transcription factors have been characterized, the peroxisome proliferator-activated receptor (PPAR) and the hepatic nuclear factor 4α. DHA also has significant effects on photoreceptor membranes involved in the signal transduction process, rhodopsin activation, and rod and cone development. Comprehensive clinical studies have shown that dietary supplementation with marine oil or single-cell oils, sources of LCPUFA, results in increased blood levels of DHA and AA, as well as an associated improvement in visual function in formula-fed premature infants to match that of human milk-fed infant. Recent clinical trials convincingly support LCPUFA supplementation of preterm infant formulations and possibly term formula to mimic human milk composition.

Keywords

Essential fatty acidsDocosahexaenoic acidPeroxisome proliferator-activated receptorGene expressionRetinal development
Type
Plenary Lecture
Information
Proceedings of the Nutrition Society , Volume 59 , Issue 1 , February 2000 , pp. 3 - 15
Copyright
Copyright © The Nutrition Society 2000

References

Ackman, RG (1964) Structural homogeneity in unsaturated fatty acids of marine lipids. A review. Journal of the Fishing Resources Board Canada 21, 247–254.CrossRefGoogle Scholar
Agostoni, C, Riva, E, Trojan, S, Bellù, R & Giovannini, M (1995a) Docosahexaenoic acid status and developmental quotient of healthy term infants. Lancet 346, 868.CrossRefGoogle ScholarPubMed
Agostoni, C, Trojan, S, Bellù, R, Riva, E, Bruzzese, MG & Giovanni, M (1997) Developmental quotient at 24 months and fatty acid composition of diet in early infancy: a follow up study. Archives of Diseases of Childhood 76, 421–424.CrossRefGoogle ScholarPubMed
Agostoni, C, Trojan, S, Bellù, R, Riva, E & Giovanni, M (1995b) Neurodevelopmental quotient of healthy term infants and feeding practice: the role of long-chain polyunsaturated fatty acids. Pediatric Research 38, 262–266.CrossRefGoogle ScholarPubMed
Akimoto, MT, Ishii, K, Yamagaki, K, Ohtagushi, K, Koide, K & Yasawa, K (1990) Production of eicosapentaenoic acid by a bacterium isolated from mackerel intestines. Journal of the American Oil Chemistry Society 67, 911–915.CrossRefGoogle Scholar
Al, MDM, Hornstra, G, Van, der Schouw YT, Bultra-Ramakers, MT & Huisjes, HJ (1990) Biochemical EFA status of mothers and their neonates after normal pregnancy. Early Human Development 24, 239–248.CrossRefGoogle ScholarPubMed
Al, MDM, Van, Houwelingen AC, Kester, AD, Hasaart, TH, Jong, EP & Honstra, G (1995) Maternal essential fatty acid pattern during normal pregnancy and their relationship to the neonatal essential fatty acid status. British Journal of Nutrition 74, 55–68.CrossRefGoogle Scholar
Amri, E, Ailhaud, G & Grimaldi, P (1991a) Regulation of adipose cell differentiation. II. Kinetics of induction of the αP2 gene by fatty acids and modulation by dexamethasone. Journal of Lipid Research 32, 1457–1463.CrossRefGoogle Scholar
Amri, E, Bertrand, B, Ailhaud, G & Grimaldi, P (1991b) Regulation of adipose cell differentiation. I. Fatty acids are inducers of aP2 gene expression. Journal of Lipid Research 32, 1449–1456.Google Scholar
Aoyama, T, Peters, JM, Iritani, N, Nakajima, T, Furihata, K, Hashimoto, T & González, FJ (1998) Altered constitutive expression of fatty acid-metabolizing enzymes in mice lacking the peroxisome proliferator-activated receptor α. Journal of Biological Chemistry 273, 5678–5684.CrossRefGoogle ScholarPubMed
Auestad, N, Montaldo, M, Hall, R, Fitzgerald, KH, Wheeler, RE, Connor, WE, Neuringer, M, Connor, SL, Taylor, JA & Hartmann, EE (1997) Visual acuity, erythrocyte fatty acid composition, and growth in term infants fed formulas with long chain polyunsaturated fatty acid for one year. Pediatric Research 41, 1–10.CrossRefGoogle ScholarPubMed
Baur, LA, O'Connor, J, Pan, DA, Kriketos, AD & Storlien, LH (1998) The fatty acid composition of skeletal muscle membrane phospholipid: its relationship with the type of feeding and plasma glucose levels in young children. Metabolism 47, 106–112.CrossRefGoogle ScholarPubMed
Birch, EE, Birch, DG, Hoffman, DR & Uauy, RD (1992) Retinal development in very low birth weight infants fed diets differing in omega-3 fatty acids. Investigative Ophthalmology and Visual Science 33, 2365–2376.Google ScholarPubMed
Birch, EE, Hoffman, DR, Uauy, R, Birch, DG & Prestidge, C (1998) Visual acuity and the essentiality of docosahexaenoic acid and arachidonic acid in the diet of term infants. Pediatric Research 44, 1–9.CrossRefGoogle ScholarPubMed
Bourre, JM, Dihn, L, Boithias, C, Dumont, O, Piciotti, M & Cunnane, S (1997) Possible role of the choroid plexus in the supply of brain tissue with polyunsaturated fatty acids. Neuroscience Letters 224, 1–4.CrossRefGoogle ScholarPubMed
Bourre, JM, Durand, G, Pascal, G & Youyou, A (1989a) Brain cell and tissue recovery in rats made deficient in n-3 fatty acids by alteration of dietary fat. Journal of Nutrition 119, 15–22.CrossRefGoogle ScholarPubMed
Bourre, JM, Francois, M, Youyou, A, Dumont, A, Piciotti, M, Pascal, G & Durand, D (1989b) The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning task in rats. Journal of Nutrition 119, 1880–1892.CrossRefGoogle Scholar
Brown, PJ, Smith-Oliver, TA, Charifson, PS, Tomkinson, NC, Fivush, AM, Sternbach, DD, Wade, LE, Orband-Miller, L, Parke, DJ, Blanchard, SG, Kliewer, SA, Lehmann, JM & Willson, TM (1997) Identification of peroxisome proliferator-activated receptor ligands from a biased chemical library. Chemical Biology 4, 909–918.CrossRefGoogle ScholarPubMed
Byard, RW, Makrides, M, Need, M, Neumann, MA & Gibson, RA (1995) Sudden infant death syndrome: Effect of breast and formula feeding on frontal cortex and brainstem lipid composition. Journal of Paediatrics and Child Health 31, 14–16.CrossRefGoogle ScholarPubMed
Calder, PC (1997) N-3 polyunsaturated fatty acids and cytokine production in health and disease. Annals of Nutrition and Metabolism 41, 203–234.Google Scholar
Caldwell, MD, Johnson, HT & Othersen, HB (1972) Essential fatty acids deficiency in an infant receiving prolonged parenteral alimentation. Journal of Pediatrics 81, 894–898.CrossRefGoogle Scholar
Carlson, SE, Ford, AJ, Werkman, SH, Peebles, JM & Koo, WWK (1996) Visual acuity and fatty acids status of term infants fed human milk and formulas with or without docosahexaenoate and arachinodate from egg yolk lecithin. Pediatric Research 39, 882–888.CrossRefGoogle ScholarPubMed
Carlson, SE, Werkman, SH, Peeples, JM, Cooke, RJ & Tolley, EA (1993) Arachidonic acid status correlates with first year growth in preterm infants. Proceedings of the National Academy of Sciences USA 90, 1073–1077.Google Scholar
Carlson, SE, Werkman, H & Tolley, E (1996b) Effect of long-chain n-3 fatty acid supplementation on visual acuity and growth of preterm infants with and without broncho- pulmonary dysplasia. American Journal of Clinical Nutrition 63, 687–697.Google Scholar
Carnielli, VP, Wattimena, DJL, Luijendijk, HT, Boerlage, A, Degenhart, HJ & Sauer, PJJ (1996) The very low birth weight premature infant is capable of synthesizing arachidonic and docosahexaenoic acids from linoleic and linolenic acids. Pediatric Research 40, 169–174.Google Scholar
Caster, WO & Ahn, P (1963) Electrocardiographic notching in rats deficient in EFA. Science 139, 1213.CrossRefGoogle Scholar
Charnok, JS (1991) Antiarrhythmic effects of fish oils. World Review of Nutrition and Dietetics 66, 278–291.CrossRefGoogle Scholar
Cho, HP, Nakamura, MT & Clarke, SD (1999) Cloning, expression, and nutritional regulation of the mammalian delta 6-desaturase. Journal of Biological Chemistry 274, 471–477.Google Scholar
Clandinin, MT, Chappell, JE, Leong, S, Heim, T, Swyer, PR & Chance, GW (1980) Intrauterine fatty acid accretion rates in human brain: implication for fatty acid requirements. Early Human Development 4, 121–130.CrossRefGoogle ScholarPubMed
Clarke, SD & Jump, DB (1993) Fatty acid regulation of gene expression: a unique role for polyunsaturated fats. In Nutrition and Gene Expression, pp. 227–246 [Berdanier, C and Hargrove, JL, editors]. Boca Raton, FL: CRC Press.Google Scholar
Clarke, DB & Jump, DD (1994) Dietary polyunsaturated fatty acid regulation of gene transcription. Annual Review of Nutrition 14, 83–98.Google Scholar
Cohen, Z, Norman, HA & Heimer, YM (1995) Microalgae as a source of n-3 fatty acids. World Review of Nutrition and Dietetics 77, 1–31.CrossRefGoogle Scholar
Cook, HW (1978) In vitro formation of PUFA by desaturation in rat brain: some properties of the enzymes in developing brain and comparison with liver. Journal of Neurochemistry 30, 1327–1334.Google Scholar
Danesch, U, Weber, PC & Sellmayer, A (1994) Arachidonic acid increases c-fos and Erg-1 mRNA in 3T3 fibroblasts by formation of PGE2 and activation of protein C. Journal of Biological Chemistry 269, 27258–27263.CrossRefGoogle Scholar
Demmelmair, H, Schenck, UV, Behrendt, E, Sauerwald, T & Koletzko, B (1995) Estimation of arachidonic acid synthesis in full term neonates, using natural variation of 13C content. Journal of Pediatric Gastroenterology and Nutrition 21, 31–36.Google Scholar
Dreyer, C, Keller, H, Mahfaudi, A, Laudet, V, Krey, G & Wahli, W (1993) Positive regulation of the peroxisomal beta-oxidation pathway by fatty acids through activation of peroxisome proliferator-activated receptor (PPAR). Biology of the Cell 77, 67–76.CrossRefGoogle Scholar
Dutta Roy, AK (1997) Fatty acid transport and metabolism in the feto placental unit and the role of fatty acid binding protein. Journal of Nutrition and Biochemistry 8, 548–557.CrossRefGoogle Scholar
Fagan, JF III (1984) The relationship of novelty preferences during infancy to later intelligence and later recognition memory. Intelligence 8, 339–346.Google Scholar
Farquharson, J, Cockburn, F, Patrick, WA, Jamieson, EC & Logan, RW (1992) Infant cerebral cortex phospholipid fatty-acid composition and diet. Lancet 340, 810–813.CrossRefGoogle ScholarPubMed
Farquharson, J, Jamieson, EC, Logan, RW, Patrick, WA, Howatson, AG & Cockburn, F (1995) Age- and dietary-related distributions of hepatic arachidonic and docosahexaenoic acid in early infancy. Pediatric Research 38, 361–365.CrossRefGoogle ScholarPubMed
Fernandez, G & Venkatraman, JT (1993) Role of omega 3 fatty acids in health and disease. Nutrition Research 13, S19–S45.CrossRefGoogle Scholar
Folsom, AR, Ma, J, McGovern, P & Eckfeldt, JH (1996) Relation between plasma phospholipid saturated fatty acids and hyperinsulinemia. Metabolism 45, 223–228.CrossRefGoogle ScholarPubMed
Foreman-van Drogelen, MM, Al, MD, Van, Houweligen AC, Blanco, CE & Honstra, G (1995) Comparison between the essential fatty acid status of preterm and full-term infants, measured in umbilical vessels. Early Human Development 42, 241–251.Google Scholar
Gibson, R, Neumann, M & Makrides, M (1997) Effect of increasing breast milk docosahexaenoic acid on plasma and erythrocyte phospholipid fatty acids and neural indices of exclusively breast fed infants. European Journal of Clinical Nutrition 51, 578–584.CrossRefGoogle ScholarPubMed
Gottlicher, M, Demoz, A, Svenson, D, Tollet, P, Berge, RK & Gustaffson, JA (1993) Structural and metabolic requirements for activators of the peroxisome proliferator-activated receptor. Biochemical Pharmacology 46, 2177–2184.Google Scholar
Grimaldi, PA, Knobel, SM, Whitesell, R & Abumrad, NA (1992) Induction of the αP2 gene by nonmetabolized long chain fatty acids. Proceedings of the National Academy of Sciences USA 89, 10930–10934.Google Scholar
Hallaq, H, Smith, T & Leal, A (1992) Modulation of dihydropyridine-sensitive calcium channels in heart cells by fish oil fatty acids. Proceedings of the National Academy of Sciences USA 89, 1760–1764.CrossRefGoogle ScholarPubMed
Hansen, AE, Wiese, HF, Boelsche, AN, Haggard, ME, Adam, DJD & Davis, H (1963) Role of linoleic acid in infant nutrition: clinical and chemical study of 428 infants fed on milk mixtures varying in kind and amount of fat. Pediatrics 31, 171–192.CrossRefGoogle Scholar
Hertz, R, Magenheim, J, Berman, I & Bar-Tana, J (1998) Fatty acyl-CoA thioesters are ligands of hepatic nuclear factor-4α. Nature 392, 512–516.Google Scholar
Hoffman, DR, Birch, EE, Birch, DG & Uauy, R (1999) Fatty acid profile of buccal cheek cell phospholipids as an index for dietary intake of docosahexaenoic acid in preterm infants. Lipids 34, 337–342.Google Scholar
Holh, CM & Rosen, P (1987) The role of arachidonic acid in rat heart cell metabolism. Biochimica et Biophysica Acta 921, 356–363.Google Scholar
Holman, RT, Johnson, SB & Hatch, TF (1982) A case of human linolenic acid deficiency involving neurological abnormalities. American Journal of Clinical Nutrition 35, 617–623.CrossRefGoogle ScholarPubMed
Honstra, G, Al, MDM, Van Houwelingen, AC & Foreman-van Drongelen, MM (1996) Essential fatty acids, pregnancy and pregnancy outcome. In Recent Development in Infant Nutrition, pp. 51–63 [Bindels, JC, Goededhart, AC and Visser, HKA, editors]. London: Kluwer Academic Publishers.CrossRefGoogle Scholar
Ibrahimi, A, Teboul, L, Gaillard, D, Amri, EZ, Ailhaud, G, Young, P, Cawthorne, MA & Grimaldi, PA (1994) Evidence for a common mechanism of action for fatty acids and thiazolidinedione antidiabetic agents on gene expression in preadipose cells. Molecular Pharmacology 46, 1070–1076.Google Scholar
Innis, SM (1992) Human milk and formula fatty acids. Journal of Pediatrics 120, S56–S61.CrossRefGoogle ScholarPubMed
Iwamoto, H & Sato, G (1986) Production of EPA by freshwater unicellular algae. Journal of the American Oil Chemistry Society 63, 434–438.Google Scholar
Jensen, C, Prager, T, Fraley, J, Chen, H, Anderson, R & Heird, W (1997) Functional effects of dietary linoleic/linolenic acid ratio in term infants. Journal of Pediatrics 130, 200–204.Google Scholar
Jensen, RG (1996) The lipids in human milk. Progress in Lipids Research 35, 53–92.Google Scholar
Kang, JX & Leaf, A (1995) Prevention and termination of the beta-adrenergic agonist-induced arrhythmia by free polyunsaturated fatty acids in neonatal rat cardiac myocytes. Biochemical and Biophysical Research Communications 208, 629–636.Google Scholar
Kimura, R (1998) Lipid metabolism in the fetal-placental unit. In Principles of Perinatal Neonatal Metabolism, pp. 389–402 [Cowett, R, editor]. New York: Springer-Verlag.CrossRefGoogle Scholar
Kliewer, SA, Lenhard, JM, Willson, TM, Patel, J, Morris, DC & Lehman, JM (1995) A prostaglandin J2 metabolite binds peroxisome proliferator activated receptor gamma and promotes adipocyte differentiation. Cell 83, 813–819.Google Scholar
Kliewer, SA, Sundsett, SS, Jones, SA & Brown, PJ (1997) Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator activated receptor alpha and gamma. Proceedings of the National Academy of Sciences USA 94, 4318–4323.CrossRefGoogle Scholar
Leaf, A & Kang, JX (1997) Dietary n-3 fatty acids in the prevention of lethal cardiac arrhythmias. Current Opinion in Lipidology 8, 4–6.CrossRefGoogle ScholarPubMed
Lee, AG, East, JM & Froud, RJ (1986) Are essential fatty acids essential for membrane function? Progress in Lipid Research 25, 41–46.Google Scholar
Lin, DS, Connor, WE, Anderson, GJ & Neuringer, M (1990) Effects of dietary n-3 fatty acids on the phospholipid molecular species of monkey brain. Journal of Neurochemistry 55, 1200–1207.CrossRefGoogle ScholarPubMed
Litman, BL & Mitchell, DC (1996) A role for phospholipids polyunsaturation in modulating membrane protein function. Lipids 31, S139–S197.CrossRefGoogle ScholarPubMed
Love, JA, Saurn, WR & McGee, R (1985) The effects of exposure to exogenous fatty acids and membrane fatty acid modification on the electrical properties of NG108–15 cells. Cellular and Molecular Neurobiology 5, 333–352.CrossRefGoogle ScholarPubMed
Makrides, M, Neumann, M, Simmer, K, Pater, J & Gibson, R (1995a) Are long-chain polyunsaturated fatty acids essential nutrients in infancy? Lancet 345, 1463–1468.Google Scholar
Makrides, M, Simmer, K, Neumann, M & Gibson, R (1995b) Changes in the polyunsaturated fatty acids of breast milk from mothers of full-term infants over 30 wk of lactation. American Journal of Clinical Nutrition 61, 1231–1233.CrossRefGoogle ScholarPubMed
Martinez, M & Vazquez, E (1998) MRI evidence that docosahexaenoic acid ethyl ester improves myelination in generalized peroxisomal disorders. Neurology 51, 26–32.CrossRefGoogle ScholarPubMed
Menon, NK & Dhopeshwarkar, GA (1982) Essential fatty acid deficiency and brain development. Progress in Lipid Research 21, 309–326.CrossRefGoogle ScholarPubMed
Mitchell, DC, Straume, M & Litman, BJ (1992) Role of sn-1-saturated, sn-2-polyunsaturated phospholipids in control of membrane receptor conformational equilibrium: Effects of cholesterol and acyl chain unsaturation on the metarhodopsin I equilibrium with metarhodopsin II. Biochemistry 31, 662–670.CrossRefGoogle ScholarPubMed
Nagy, L, Tonotoz, P, Alvarez, JG, Chen, H & Evans, RM (1998) Oxidized LDL regulates macrophage gene expression through ligand activation of PPAR gamma. Cell 93, 229–240.CrossRefGoogle Scholar
Neuringer, M, Connor, WE, Van, Petten C & Barstad, L (1984) Dietary omega-3 fatty acid deficiency and visual loss in infant rhesus monkeys. Journal of Clinical Investigation 73, 272–276.Google Scholar
Okuno, M, Kajiwara, K, Imai, S, Kobayashi, T, Honma, N, Maki, T, Suruga, K, Godat, T, Takase, S, Muto, Y & Moriwaki, H (1997) Perilla oil prevents the excessive growth of visceral adipose tissue in rats by down regulating adipocyte differentiation. Journal of Nutrition 127, 1752–1757.CrossRefGoogle ScholarPubMed
Olsen, S, Sorensen, J, Secher, N, Hedegaard, M, Henriksen, TB, Hansen, HS & Grant, A (1992) Randomized controlled trial of effect of fish oil supplementation on pregnancy duration. Lancet 339, 1003–1007.CrossRefGoogle ScholarPubMed
Ongari, MA, Ritter, JM, Orchard, MA, Waddell, KA, Blair, IA & Lewis, PJ (1984) Correlation of prostacyclin synthesis by human umbilical artery with status of essential fatty acid. American Journal of Obstetrics and Gynecology 149, 455–460.Google Scholar
Otto, SJ, Van, Houwelingen AC, Antal, M, Manninen, A, Godfrey, K, López-Jaramillo, P & Honstra, G (1997) Maternal and neonatal essential fatty acid status in phospholipids: an international comparative study. European Journal of Clinical Nutrition 51, 232–242.CrossRefGoogle ScholarPubMed
Pegorier, JP, Chatelain, F, Thumelin, S & Girard, J (1998) Role of long-chain fatty acids in the postnatal induction of genes coding for liver mitochondrial β-oxidative enzymes. Biochemical Society Transactions 26, 113–120.Google Scholar
Reece, M, McGregor, J, Allen, K & Harris, MA (1997) Maternal and perinatal long-chain fatty acids: Possible roles in preterm birth. American Journal of Obstetrics and Gynecology 176, 907–914.CrossRefGoogle ScholarPubMed
Ristow, M, Müller-Wieland, D, Pfeiffer, A, Wilhem, Krone C & Kahn, R (1998) Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. New England Journal of Medicine 339, 953–959.CrossRefGoogle Scholar
Rotstein, NP, Politi, LE & Aveldaño, MI (1998) Docosahexaenoic acid promotes differentiation of developing photoreceptors in culture. Investigative Ophthalmology and Visual Science 39, 2750–2758.Google Scholar
Rodriguez de Turco, EB, Deretic, D, Bazan, NG & Papermaster, DS (1997) Post Golgi vesicles cotransport docosahexaenoyl phospholipids and rhodopsin during frog photoreceptor membranes biogenesis. Journal of Biological Chemistry 272, 10494–10497.Google ScholarPubMed
Salem, N, Shingu, T, Kim, HY, Hullin, F, Bougnoux, P & Karanian, JW (1988) Specialization in membrane structure and metabolism with respect to polyunsaturated lipids. In Biological Membranes: Aberrations in Membrane Structure and Function, pp. 319–333 [Karnovsky, ML, Leaf, A and Bollis, LC, editors]. New York: Alan R. Liss.Google Scholar
Salem, N, Wegher, B, Mena, P & Uauy, R (1996) Arachidonic and docosahexaenoic acids are biosynthesized from the 18-carbon precursors in human infants. Proceedings of the National Academy of Sciences USA 93, 49–54.CrossRefGoogle ScholarPubMed
Sauerwald, T, Hachey, D, Jensen, CL, Chen, H, Anderson, RE & Heird, WC (1997) Intermediates in endogenous synthesis of C22: n-3 and C20: n-6 by term and preterm infants. Pediatric Research 441, 183–187.CrossRefGoogle Scholar
Sawatzki, G, Georgi, G & Kohn, G (1994) Pitfalls in the design and manufacture of infant formulae. Acta Paediatrica 402, Suppl., 40–45.Google Scholar
Sellmayer, A, Danesch, U & Weber, PC (1996) Effects of different polyunsaturated fatty acids on growth-related early gene expression and cell growth. Lipids 31, S37–S40.CrossRefGoogle ScholarPubMed
Sheaff, Greiner RC, Winyer, J, Nathanielsz, PW & Brenna, JT (1997) Brain docosahexaenoate accretion in fetal baboons: bioequivalence of dietary alpha linolenic and docosahexaenoic acids. Pediatric Research 42, 826–834.Google Scholar
Simopoulos, AP & Salem, N (1992) Egg yolk as a source of long-chain polyunsaturated fatty acids in infant feeding. American Journal of Clinical Nutrition 55, 411–414.Google Scholar
Slater, A (1995) Individual differences in infancy and later IQ. Journal of Child Psychology and Psychiatry 36, 69–112.Google Scholar
Sprecher, H (1981) Biochemistry of essential fatty acids. Progress in Lipid Research 20, 13–22.Google Scholar
Stubbs, CD & Smith, AD (1984) The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function. Biochimica et Biophysica Acta 779, 89–137.CrossRefGoogle ScholarPubMed
Tontonoz, P, Hu, EH, Graves, RA, Budavari, AI & Spiegelman, BM (1994) MPPAR-γ2: tissue-specific regulator of an adipocyte enhancer. Genes and Development 8, 1224–1234.Google Scholar
Treen, M, Uauy, R, Jameson, D, Thomas, VL & Hoffman, DR (1992) Effect of docosahexaenoic acid on membrane fluidity and function in intact cultured Y-79 retinoblastoma cells. Archives of Biophysics 294, 564–570.CrossRefGoogle ScholarPubMed
Uauy, R, Birch, DG, Birch, EE, Tyson, JE & Hoffman, DR (1990) Effect of dietary omega 3 fatty acids on retinal function of very low birth weight neonates. Pediatric Research 28, 485–492.Google Scholar
Uauy, R, Peirano, P, Hoffmann, D, Mena, P, Birch, D & Birch, E (1996) Role of essential fatty acids in the function of the developing nervous system. Lipids 31, S-167–S-176.Google Scholar
Van Houwelingen, AC, Foreman-van Drongelen, MM, Nicolini, U, Nicolaides, KH, Al, MDM, Kester, ADM & Honstra, G (1996) Essential fatty acids status of fetal plasma phospholipids: similar to postnatal values obtained at comparable gestational ages. Early Human Development 46, 141–152.Google Scholar
Voskuyl, RA, Vreugdenhil, M, Kang, JX & Leaf, A (1998) Anticonvulsant effect of polyunsaturated fatty acids in rats, using the cortical stimulation model. European Journal of Pharmacology 341, 145–152.Google Scholar
Voss, A, Reinhart, M, Shankarappa, S & Sprecher, H (1991) The metabolism of 7,10,13,16,19-docosapentaenoic acid to 4,7,10,13,16,19-docosahexaenoic acid in the rat liver is independent of a 4-desaturase. Journal of Biological Chemistry 266, 19995–20000.Google Scholar
Vreugdenhil, M, Bruehl, C, Voskuyl, RA, Kang, JX, Leaf, A & Wadman, WJ (1996) Polyunsaturated fatty acids modulate sodium and calcium currents in CA1 neurons. Proceedings of the National Academy of Sciences USA 93, 12559–12563.Google Scholar
Weidmann, TS, Pates, RD, Beach, JM, Salmon, A & Brown, MF (1988) Lipid-protein interactions mediate the photochemical function of rhodopsin. Biochemistry 27, 6469–6474.Google Scholar
Whelan, J (1996) Antagonistic effects of dietary arachidonic acid and n-3 polyunsaturated fatty acids. Journal of Nutrition 126, 1086S–1091S.Google Scholar
Werkman, SH & Carlson, SE (1996) A randomized trial of visual attention of preterm infants fed docosahexaenoic acid until nine months. Lipids 31, 91–97.CrossRefGoogle ScholarPubMed
Weylandt, KH, Kang, JX & Leaf, A (1996) Polyunsaturated fatty acids exert anti arrhythmic actions as free acids rather than in phospholipids. Lipids 31, 977–982.Google Scholar
Wheeler, TG, Benolken, RM & Anderson, RE (1975) Visual membranes: specificity of fatty acid precursors for the electrical response to illumination. Science 188, 1312–1314.CrossRefGoogle ScholarPubMed
Willats, P, Forsyth, J, DiModugno, M, Varma, S & Colvin, M (1998) Effect of long-chain polyunsaturated fatty acids in infant formula on problem solving at 10 months of age. Lancet 352, 688–691.CrossRefGoogle Scholar
Yorek, MA, Bohnker, RR, Dudley, DT & Ginsberg, B (1984) Comparative utilization of n-3 polyunsaturated fatty acids by cultures of human Y-79 retinoblastoma cells. Biochimica et Biophysica Acta 795, 277–285.Google Scholar
Yu, K, Bayona, W, Kallen, CB, Harding, HP, Ravera, CP, MacMahon, G, Brown, M & Lazar, MA (1995) Differential activation of peroxisome proliferator activated receptor by eicosanoids. Journal of Biological Chemistry 270, 23975–23983.Google Scholar