Enzymes of Fatty Acid β‐Oxidation in Developing Brain (original) (raw)
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Neuroscience Letters, 1999
The developmental changes of microsomal 3-hydroxyacyl-CoA dehydrase and trans-2,3-enoyl-CoA reductase activities were analyzed and compared to very-long-chain fatty acid content and biosynthesis in rat brain. Contrary to the elongation rate of eicosanoyl-CoA and 3-hydroxyeicosanoyl-CoA, which paralleled myelination during brain maturation, the two partial activities of fatty acid elongation were already present at the earliest stages of development. One day after birth, 3-hydroxyacyl-CoA dehydrase and trans-2,3-enoyl-CoA reductase specific activities already represented 54.8% and 49.6% of the adult values, respectively. As a contribution to the quantitative estimation of the brain's ability to form its own VLCFA, it is shown that dehydrase and reductase activities are sufficient to allow the biosynthesis of all rat brain VLCFA at any age.
Incorporation of chylomicron fatty acids into the developing rat brain
Journal of Clinical Investigation, 1994
The developing brain obtains polyunsaturated fatty acids from the circulation, but the mechanism and route of delivery of these fatty acids are undetermined. '4C-labeled chylomicrons were prepared by duodenal infusion of I1-'4C116:0, 11-'4C118:2(n-6), I1-'4C118:3(n-3), or I1-14C122:6(n-3) into adult donor rats, and were individually injected into hepatectomized 2-wk-old suckling rats. After minor correction for trapped blood in the brain, the incorporation of chylomicron fatty acids after 30 min was nearly half that of a coinjected free fatty acid reference. 11-14C122:6(n-3)-labeled chylomicrons showed an average 65% greater incorporation than chylomicrons prepared from the other fatty acids. This apparent selectivity may have been partly due to lower oxidation of 22:6(n-3) in the brain compared to the other fatty acids tested, based on recovered water-soluble oxidation products. The bulk of the radioactivity in the brain was found in phospholipid and triacylglycerol, except that animals injected with 1-14C122:6(n-3) chylomicrons showed considerable incorporation also into the fatty acid fraction instead of triacylglycerol. These data show that chylomicrons may be an important source of fatty acids for the developing rat brain.
Elongation, desaturation, and esterification of essential fatty acids by fetal rat brain in vivo
The Journal of Lipid Research, 1994
Tracer amounts of either [l-14C]linolenic (18:3n-3, LNA), or [ l-~*C]linoleic (18:2n-6, LA) acids were intracranially injected into 19-to 20-day-old rat fetuses, and the time course of the in vivo formation and esterification of their long chain polyenoic metabolites was determined for up to 20 h. A rapid disappearance of free LNA and LA, with apparent half-lives of 60 and 40 min, respectively, was noticed. One hour after LNA injection, 32.3% and 14.3% of the total brain radioactivity was found in the neutral glyceride (NG) and phospholipid (PL) fractions, respectively. After 20 h, PL radioactivity attained a level of 75%. Phosphatidylcholine (PC), diacylglycerol (DG), and
Role of essential fatty acids in the function of the developing nervous system
Lipids, 1996
The basis for n-3 fatty acid essentiality in humans includes not only biochemical evidence but functional measures associated with n-3 deficiency in human and nonhuman primates. Functional development of the retina and the occipital cortex are affected by α-linolenic acid deficiency and by a lack of docosahexaenoic acid (DHA) in preterm infant formulas and, as reported more recently, in term diets. Functional effects of n-3 supply on sleep-wake cycles and heart rate rhythms support the need for dietary n-3 fatty acids during early development. Our results indicate that n-3 long-chain polyunsaturated fatty acids should be considered provisionally essential for infant nutrition. DHA may also be required by individuals with inherited metabolic defects in elongation and desaturation activity, such as patients with peroxisomal disorders and some forms of retinitis pigmentosa.
Journal of Lipid Research, 1999
Information on the prenatal accumulation of rat brain membrane lipids is scarce. In this study we investigated in detail the fatty acid (FA) composition of the rat brain, on each day from embryonic day 12 (E12) up to birth, and on 8 time points during the first 16 days of postnatal life, and correlated the FA changes with welldescribed events of neurogenesis and synaptogenesis. Between E14 and E17, there was a steep increase in the concentration of all the FAs: 16:0 increased by 136%, 18:0 by 139%, 18:1 by 92%, 20:4n-6 by 98%, 22:4n-6 by 116%, 22:5n-6 by 220%, and 22:6n-3 by 98%. After this period and up to birth, the concentration of the FAs plateaued, except that of 22:6n-3, which accumulated further, reaching an additional increase of 75%. After birth, except 22:5n-6, all FAs steadily increased at various rates. Estimation of the FA/PL molar ratios showed that prenatally the ratios of all the FAs either decreased or remained constant, but that of 22:6n-3 increased more than 2-fold; postnatally the ratios remained constant, with the exception of 22:4n-6 and 22:5n-6, which decreased. In conclusion, prenatal accumulation of brain fatty acids parallels important events in neurogenesis. 22:6n-3 is exceptional inasmuch in its steep accumulation occurs just prior to synaptogenesis.-Green, P., S. Glozman, B. Kamensky, and E. Yavin. Developmental chantes in rat brain membrane lipids and fatty acids: the preferential prenatal accumulation of docosahexaenoic acid.
Essential fatty acids and the brain: possible health implications
International Journal of Developmental Neuroscience, 2000
Linoleic and a-linolenic acid are essential for normal cellular function, and act as precursors for the synthesis of longer chained polyunsaturated fatty acids (PUFAs) such as arachidonic (AA), eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), which have been shown to partake in numerous cellular functions aecting membrane¯uidity, membrane enzyme activities and eicosanoid synthesis. The brain is particularly rich in PUFAs such as DHA, and changes in tissue membrane composition of these PUFAs re¯ect that of the dietary source. The decline in structural and functional integrity of this tissue appears to correlate with loss in membrane DHA concentrations. Arachidonic acid, also predominant in this tissue, is a major precursor for the synthesis of eicosanoids, that serve as intracellular or extracellular signals. With aging comes a likely increase in reactive oxygen species and hence a concomitant decline in membrane PUFA concentrations, and with it, cognitive impairment. Neurodegenerative disorders such as Parkinson's and Alzheimer's disease also appear to exhibit membrane loss of PUFAs. Thus it may be that an optimal diet with a balance of n-6 and n-3 fatty acids may help to delay their onset or reduce the insult to brain functions which these diseases elicit. Published by
Brain Research, 2008
Docosahexaenoic acid (DHA, 22:6ω-3) is a major polyunsaturated fatty acid in the brain and is required in large amounts during development. Low levels of DHA in the brain are associated with functional deficits. The ω-3 fatty acids are essential nutrients and their metabolism and incorporation in developing brain depends on the composition of dietary fat. We assessed the importance of the intake of the ω-3 fatty acid, 18:3ω-3 and the balance with the ω-6 fatty acid, 18:2ω-6, and the effects of dietary arachidonic acid (20:4ω-6) and DHA in milk diets using the piglet as a model of early infant nutrition. Piglets were fed (% energy) 1.2% 18:2ω-6 and 0.05% 18:3ω-3 (deficient), 10.7% 18:2ω-6 and 1.1% 18:3ω-3 (contemporary), 1.2% 18:2ω-6 and 1.1% 18:3ω-3 (evolutionary), or the contemporary diet with 0.3% 20:4ω-6 and 0.3% DHA (supplemented) from birth to 30 days of age. Our results show that a contemporary diet, high in 18:2ω-6 compromises DHA accretion and leads to increased 22:4ω-6 and 22:5ω-6 in the brain. However, an evolutionary diet, low in 18:2ω-6, supports high brain DHA. DHA supplementation effectively increased DHA, but not the intermediate ω-3 fatty acids, 20:5ω-3 and 22:5ω-3. Using primary cultures of cortical neurons, we show that 22:5ω-6 is efficiently acylated and preferentially taken up over DHA. However, DHA, but not 22:5ω-6 supports growth of secondary neurites. Our results suggest the need to consider whether current high dietary ω-6 fatty acid intakes compromise brain DHA accretion and contribute to poor neurodevelopment.
Journal of Neurochemistry, 1984
Rats were fed through four generations with a semisynthetic diet containing 1 .O% sunflower oil (6.7 mg/ g n-6 fatty acids, 0.04 mgig n-3 fatty acids). Ten days before mating, half of the animals received a diet in which sunflower was replaced by soya oil (6.6 mg/g n-6 fatty acids, 0.8 mg/g n-3 fatty acids) and analyses were performed on their pups. Fatty acid analysis in isolated cellular and subcellular material from sunflower-fed animals showed that the total amount of unsaturated fatty acids was not reduced in any cellular or subcellular fraction (except in 60-day-old rat neurons). All material from animals fed with sunflower oil showed an important reduction in the docosahexaenoic acid content, compensated (except in 60-day-old rat neurons) by an increase in the n-6 fatty acids (mainly C22:S n-6). When comparing 60-day-old animats fed with soya oil or sunflower oil, the n-31n-6 fatty acid ratio was reduced 16-fold in oligodendrocytes, 12-fold in myelin, twofold in neurons, sixfold in synaptosomes, and threefold in astrocytes. No trienes were detected. Saturated and monounsaturated fatty acids were hardly affected. This study provides data on the fatty acid composition of isolated brain cells. Key Words: Neurons-Astrocytes-Oligodendrocytes-Myelin-Synaptosomes-n-3 Fatty acids-Diet. Bourre J. M. et al. Alterations in the fatty acid composition of rat brain cells (neurons, astrocytes, and oligodendrocytes) and of subcellular fractions (myelin and synaptosomes) induced by a diet devoid of n-3 fatty acids. . (1971) Brain recovery from essential fatty acid deficiency in developing rats. J . Neurochem. 18, 869-882. 175-184.