N-3 Polyunsaturated fatty acids deficiency

Delion S, Chalon S, Guilloteau D, Lejeune B, Besnard JC, Durand G. Age-related changes in phospholipid fatty acid composition and monoaminergic neurotransmission in the hippocampus of rats fed a balanced or an n-3 polyunsaturated fatty acid deficient diet. J Lipid Res 1997 38 680-689. 

Zimmer L, Delpal S, Guilloteau D, Aioun J, Durand G, Chalon S. Chronic n-3 polyunsaturated fatty acid deficiency alters dopamine vesicle density in the rat frontal cortex. Neurosci Lett 2000 284f 1—2) 25—28. 

Zimmer, L., Durand, G., Guilloteau, D., and Chalon, S. 1999. n-3 polyunsaturated fatty acid deficiency and dopamine metabolism in the rat frontal cortex. Lipids, 34 Suppl, S251. 

Zimmer L., Delion-Vancassel S., Durand G., Guilloteau D., Bodard S., Besnard J. C., and Chalon S. (2000). Modification of dopamine neurotransmission in the nucleus accumbens of rats deficient in n-3 polyunsaturated fatty acids. J. Lipid Res. 41 32 10. 

Watanabe S, Doshi M, Hamazaki T (2003) n-3 Polyunsaturated fatty acid (PUFA) deficiency elevates and n-3 PUFA enrichment reduces brain 2-arachidonoylglycerol level in mice. Prostaglandins Leukot Essent Fatty Acids 69 51-59... 

Zimmer L, Hembert S, Durand G. Guilloteau D, Bodard S, Besnard JC, et al. Chronic n-3 polyunsaturated fatty acid diet-deficiency acts on dopamine metabolism in the rat frontal cortex a micro-dialysis study. Neurosci Lett 1998 240 177-181. 

Brunengraber H. Potential of ketone body esters for parenteral and oral nutrition. Nutrition 1997 13 233-235. Carrie 1, Clement M, Javel DD, Frances H, Bourre J. Learning deficits in first generation OFl mice deficient in (n-3) polyunsaturated fatty acids do not result from visual alteration. Neurosci Lett 1999 266 69-72. 

FIGURE 3-7 Pathways for the interconversion of brain fatty acids. Palmitic acid (16 0) is the main end product of brain fatty acid synthesis. It may then be elongated, desaturated, and/or P-oxidized to form different long chain fatty acids. The monoenes (18 1 A7, 18 1 A9, 24 1 A15) are the main unsaturated fatty acids formed de novo by A9 desaturation and chain elongation. As shown, the very long chain fatty acids are a-oxidized to form a-hydroxy and odd numbered fatty acids. The polyunsaturated fatty acids are formed mainly from exogenous dietary fatty acids, such as linoleic (18 2, n-6) and a-linoleic (18 2, n-3) acids by chain elongation and desaturation at A5 and A6, as shown. A A4 desaturase has also been proposed, but its existence has been questioned. Instead, it has been shown that unsaturation at the A4 position is effected by retroconversion i.e. A6 unsaturation in the endoplasmic reticulum, followed by one cycle of P-oxidation (-C2) in peroxisomes [11], This is illustrated in the biosynthesis of DHA (22 6, n-3) above. In severe essential fatty acid deficiency, the abnormal polyenes, such as 20 3, n-9 are also synthesized de novo to substitute for the normal polyunsaturated acids. 

In our previous reports, we have shown that infant rhesus monkeys born from mothers fed an n-3 fatty acid-deficient diet and then also fed a deficient diet after birth developed low levels of n-3 fatty acids in the brain and retina and impairment in visual function (Neuringer et al., 1984, Connor et al., 1984, Neuringer et al., 1986). The specific biochemical markers of the n-3-deficient state were a marked decline in the DHA of the cerebral cortex and a compensatory increase in n-6 fatty acids, especially docosapenta-enoic acid (22 5n-6). Thus, the sum total of the n-3 and n-6 fatty acids remained similar, about 50% of the fatty acids in phosphatidylethanolamine and phosphatidylserine, indicating the existence of mechanisms in the brain to conserve polyunsaturation of membrane phospholipids as much as possible despite the n-3-deficient state. 

Fig. 1. The time-course of mean fatty acid changes in plasma phospholipids after the feeding of fish oil. Note that reciprocal changes ofthe two major n-3 (EPA andDH A) and the major n-6 (18 2) polyunsaturated fatty acids occurred as n-3 fatty acids increased and n-6 fatty acids decreased. The concentrations of these fatty acids in the plasma phospholipids of monkeys fed the control soybean oil and safflower oil diet from our previous study (Neuringer et al, 1986) are given for comparison. Expressed as percentage of total fatty acids, DHA in control monkeys was 1.1 0.7% EPA 0.2 0.1% 18 2n-6, 39.6 2.3%. In deficient monkeys, DHA was 0% 18 2n-6 was 36.7 0.7%.

Fujimoto K, Kanno T, Koga 11, Gnoderqa K, Hirano H, Nishikawa M, et al. Effects of n-3 fatty acid deficiency during pregnancy and lactation on learning ability of rats. In Yasugi Y, Nakamura H, Soma M, eds. Advances in Polyunsaturated Fatty Acid Research Elsevier Scientific, Amsterdam, 1993, pp. 257-260. 

Prostaglandins are synthesized from an essential polyunsaturated fatty acid which cannot be synthesized de novo in mammalian tissues. As a result, the dietary supply of polyunsaturated acid is an important modulating factor in making the appropriate substrate available to the enzyme. The two major types of polyunsaturated fatty acids in mammals are derived from linoleic acid (the (n-6) type) and linolenic acid (the (n-3) type). Arachidonic acid (20 4n-6), derived from linoleic acid (18 2n-6), is the most common twenty-carbon polyunsaturated fatty acid in human tissues. It is an essential fatty acid in mammals, and it is a major mediator of pathophysiologic events as it is converted to the dienoic prostaglandins and thromboxanes and the tetraenoic leukotrienes [32,33]. Our daily diet usually contains appreciable amounts of grain and cereal products rich in the n-6 fatty acids, and human deficiencies of the n-6 acids are not common. 

This sequence of desaturations and elongations enables tissues to produce a variety of polyunsaturated fatty acids tailored to their needs. Because, during the course of evolution, animals have lost the ability (retained by plants) to insert double bonds in positions 12 and 15, the members of these four families (n-3, n-6, n-7, n-9) cannot be interconverted in animal tissues. Linoleic acid and its relatives are termed essential because without them animals will die. Therefore, the first member of the series has to be supplied in the diet from plant sources. Arachidonic add, the main product of the elongation and desaturation of linoleic acid, has essential fatty acid activity in that it can cure the signs of EFA deficiency described earlier but it is not essential in the human diet as long as linoleic acid is supplied, i.e. it is an essential metabolite but not an essential nutrient for man. 

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