Perinatal biochemistry and physiology of long-chain polyunsaturated fatty acids

Abstract

Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are important structural components of the central nervous system. These fatty acids are transferred across the placenta, are present in human milk, and are accumulated in the brain and retina during fetal and infant development. The high concentrations of DHA in the retina and of DHA and ARA in brain gray matter suggests that these fatty acids have important roles in retinal and neural function. Animal studies have shown that depletion of DHA from the retina and brain results in reduced visual function and learning deficits. The latter effects may be explained by changes in the membrane bilayer that alter membrane-associated receptors and signal transduction systems, ion channel activity, or direct effects on gene expression. DHA can be formed in the liver from alpha linolenic acid, but it is unclear if the rate of DHA synthesis in humans is sufficient to support optimal brain and retinal development. Although there is no evidence that the ability to form ARA from linoleic acid is limiting, supplementation with DHA reduces tissue ARA, possibly creating a conditional need for ARA in infants with a dietary intake of DHA. The amount of DHA in human milk varies widely and is positively correlated with visual and language development in breast-fed infants. Advances in understanding essential fatty acid requirements will benefit from intervention studies that use functionally relevant tests to probe the deficiency or adequacy of physiologically important pools of DHA and ARA in developing infants. (J Pediatr 2003;143:S1-S8) D ocosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (ARA, 20:4n-6) are important structural components of the highly specialized membranes lipids of the human central nervous system. 1,2 DHA is the major polyunsaturated fatty acid in the outer segments of the retina rods and cones, where it can constitute as much as 50% of the fatty acids in phosphatidylethanolamine (PE) and phosphatidylserine (PS), and as much as 80% of all the polyunsaturated fatty acids.1 These membranes are specialized for the rapid transmission of light and contain 90% to 95% of the lipid as phospholipid. The phospholipids contain unusual PE, PS, and phosphatidylcholine (PC) species in which both acyl groups are DHA. Approximately 10% of the weight of the brain, and 50% of the dry weight, is lipid. About half of this lipid is phospholipid, with approximately 20% cholesterol, 15% to 20% cerebrosides, and smaller amounts of sulphatides and gangliosides.2 The phospholipids of brain gray matter contain high proportions of DHA in PE and PS and high amounts of ARA in phosphatidylinositol (PI). ARA is also present in membrane phospholipids, particularly in PI throughout the body. Unlike other organs, the dietary essential fatty acid linoleic acid (LA, 18:2n-6) usually represents <1% of brain and retina fatty acids, and concentrations of a-linolenic acid (18:3n-3) are even lower. 2These usual characteristics of brain and retina phospholipids suggest that specific mechanisms ...

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

“…[2][3][4][5][6] DHA is obtained directly from the diet or is synthesized in the liver from its dietary precursors a-linolenic acid (a-LNA, 18:3n-3) or eicosapentaenoic acid (EPA, 20:5n-3), neither of which can be synthesized de novo in mammalian tissue. 7 Both of these fatty acids are present at low concentrations in brain.…”

Fatty acid composition of wild anthropoid primate milks

“…However, these results may also reflect a phylogenetic difference in synthesis of LCPUFA between hominoids and monkeys. The brain rapidly accumulates n-3 and n-6 PUFA, particularly 20:4n-6 and 22:6n-3, for structure and multiple functions during the last trimester of gestation and infancy (Burdge, 2004;Carlson, 2001;Innis, 2003). Indeed, Kothapalli et al (2007) demonstrate that supplementation of neonatal baboons with modest amounts of 20:4n-6 (0.64% of total fatty acids) and 22:6n-3 (0.32% or 0.96% of total fatty acids) altered the expression of over 1100 genes in the brain.…”

Human milk: maternal dietary lipids and infant development

“…The generally-accepted pathway for further metabolism of EPA to DHA is that proposed by Sprecher (1999). It involves two successive elongations of EPA to form 24:5n-3, then desaturation at position 6 to yield 24:6n-3, which is then translocated to the peroxisomes where a single cycle of b-oxidation generates 22:6n-3 (Innis, 2003). Further metabolism of n-6 fatty acids to form docosapentaenoic acid (22:5n-6) is believed to occur through an analogous pathway.…”

“…Particularly high concentrations of DHA are present in phosphatidylserine and the ethanolamine phosphoacylglycerols (ethanolamine plasmalogen and phosphatidylethanolamine (PE)) of brain grey matter and the outer segments of rod and cone photoreceptors in the retina (Innis, 2003). DHA comprises £ 80 % of the PUFA in the retina outer segment disks, and phospholipids are present in which both fatty acids are DHA.…”