Upregulated liver conversion of α-linolenic acid to docosahexaenoic acid in rats on a 15 week n-3 PUFA-deficient diet

Igarashi, Miki; DeMar, James C.; Ma, Kaizong; Chang, Lisa; Bell, Jane M.; Rapoport, Stanley I.

doi:10.1194/jlr.m600396-jlr200

Cited by 102 publications

(159 citation statements)

References 68 publications

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“…Igarashi et al (10) recently documented the depletion of liver phospholipid and triacylglycerol in C18:3ˆ3, C20:5ˆ3, C22:5ˆ3 and C22:6ˆ3 prevailing in male rats exposed for 15 weeks after weaning to a diet containing as sole long-chain polyunsaturated ˆ3 fatty acid 0.25 μmol/g C18:3ˆ3 (as distinct from 7.8 μmol/g in the control diet). The investigations conducted by these authors differed, however, in several respects from the present study.…”

Section: Discussionmentioning

confidence: 99%

The metabolic syndrome of ω3-depleted rats. I. Liver data

Malaisse

Bulur²,

Zhang³

et al. 2009

Int J Mol Med

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Abstract. Second-generation rats depleted in long-chain polyunsaturated ˆ3 fatty acids were recently proposed as a novel animal model for the metabolic syndrome. In the present study, a dietary deprivation of ˆ3 acids for 3-7 months was found sufficient to provoke in 6-week-old normal rats the same alteration of the fatty acid content and profile of liver phospholipids and triglycerides as that otherwise prevailing in the second-generation ˆ3-depleted rats, with emphasis on a severe decrease in their ˆ3 fatty acid content, alterations in the relative contribution of and ratio between selected long-chain polyunsaturated ˆ6 fatty acids, saturated and monodesaturated fatty acids and precursors of nervonic acid, and liver steatosis. When the ˆ3-depleted rats were exposed, after the first 7 months of the present experiments and for 2-4 weeks to a diet supplemented with 5% (w/w) flaxseed oil, most of these hepatic variables returned towards or beyond control values. In both the ˆ3-depleted rats and control animals, however, the eventual exposure to the flaxseed oilenriched diet failed to suppress liver steatosis and, on the contrary, provoked a further increase in liver triglyceride content. It is proposed, therefore, that the present approach represents a simple and realistic animal model to study the consequences of ˆ3-depletion. Moreover, the results suggest that to oppose such consequences, e.g. liver steatosis, it may be necessary to combine the dietary supply of ˆ3 acids with a suitable control of food intake, in both qualitative and quantitative terms.

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Section: Discussionmentioning

confidence: 99%

The metabolic syndrome of ω3-depleted rats. I. Liver data

Malaisse

Bulur²,

Zhang³

et al. 2009

Int J Mol Med

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“…30 Thus, brain AA likely originates from the diet and/or from conversion of dietary linoleic acid in the liver. [31][32][33][34] Earlier studies implicated AA as essential for growth and development, 35 but it is now recognized that AA is also extensively involved in brain signaling 36,37 via serotonergic, 38,39 glutamatergic, 40,41 dopaminergic 42,43 and cholinergic 44,45 receptor stimulation. AA and its derivatives are also ligands for several key transcriptional regulators, including peroxisomal proliferator activator receptors, 46 hepatic nuclear factor-4a, 47 prostaglandin receptors 48 and the liver X receptor, 49 collectively mediating numerous effects.…”

Section: Overview Of the Aa Cascadementioning

confidence: 99%

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

et al. 2008

Mol Psychiatry

108

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Bipolar disorder is a major medical, social and economic burden worldwide. However, the mechanisms of action of effective antibipolar disorder drugs remain elusive. In this paper, we review studies using a neuropharmacological approach in unanesthetized rats, combined with kinetic, biochemical and molecular biology techniques, showing that chronic administration of three Food and Drug Administration-approved mood stabilizers (lithium, valproate and carbamazepine) at therapeutically relevant doses, selectively target the brain arachidonic acid (AA) cascade. Whereas chronic lithium and carbamazepine decrease the binding activity of activator protein-2 and in turn the transcription, translation and activity of its AA-selective calcium-dependent phospholipase A 2 gene product, valproate appears to be a non-competitive inhibitor of long-chain acyl-CoA synthetase. The net overlapping effects of the three drugs are decreased turnover of AA but not of docosahexaenoic acid in rat brain phospholipids, and decreased brain cyclooxygenase-2 and prostaglandin E 2 . Although these observations support the hypothesis proposed by Rapoport and colleagues that the AA cascade is a common target of mood stabilizers, this hypothesis is not necessarily exclusive of other targets. Targeting the AA cascade with drugs or diet may be a useful therapeutic approach in bipolar disorder, and examining the AA cascade in patients might help in better understanding the disease.

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“…activities might be to infuse appropriate labeled fatty acid into blood, and to measure rates of oxidation or elongation/ desaturation directly in the liver, as recently published (Igarashi et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…In many countries, however, the intakes of both a-linolenic acid (ALA; C18:3 n-3) and DHA (Burdge and Calder, 2005;Denomme et al, 2005) are lower than the current dietary recommendations (Simopoulos et al, 1999). Various dietary strategies have been proposed to increase their cellular level: (i) consumption of oils rich in ALA (Harper et al, 2006), but the rate of in vivo conversion of ALA to highly unsaturated fatty acids (FA) is low (Burdge and Calder, 2005;Hussein et al, 2005), and its effective conversion to DHA in mammalian tissues, although recently quantified in the plasma of rats as 10-fold higher than brain consumption rates (Igarashi et al, 2007), is controversial (Barcelo-Coblijn et al, 2005;Lin and Salem, 2005), because of the competition of multiple substrates for D6-desaturase (D' Andrea et al, 2002); (ii) consumption -E-mail: Vincent.Rioux@agrocampus-rennes.fr of fish, fish oil or microalgae oil (Geppert et al, 2005) directly providing the long-chain (n-3) derivatives; and (iii) consumption of both ALA and long-chain (n-3) derivatives, by using, for example, products from breeding animals that have been fed with extruded linseeds (Weill et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Substitution of dietary oleic acid for myristic acid increases the tissue storage of α-linolenic acid and the concentration of docosahexaenoic acid in the brain, red blood cells and plasma in the rat

Rioux

Catheline

Beauchamp

et al. 2008

Animal

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Various strategies have been developed to increase the cellular level of (n-3) polyunsaturated fatty acids in animals and humans. In the present study, we investigated the effect of dietary myristic acid, which represents 9% to 12% of fatty acids in milk fat, on the storage of a-linolenic acid and its conversion to highly unsaturated (n-3) fatty acid derivatives. Five isocaloric diets were designed, containing equal amounts of a-linolenic acid (1.3% of dietary fatty acids, i.e. 0.3% of dietary energy) and linoleic acid (7.0% of fatty acids, i.e. 1.5% of energy). Myristic acid was supplied from traces to high levels (0%, 5%, 10%, 20% and 30% of fatty acids, i.e. 0% to 6.6% of energy). To keep the intake of total fat and other saturated fatty acids constant, substitution was made with decreasing levels of oleic acid (76.1% to 35.5% of fatty acids, i.e. 16.7% to 7.8% of energy) that is considered to be neutral in lipid metabolism. After 8 weeks, results on physiological parameters showed that total cholesterol and low-density lipoprotein-cholesterol did not differ in the diets containing 0%, 5% and 10% myristic acid, but were significantly higher in the diet containing 30% myristic acid. In all the tissues, a significant increasing effect of the substitution of oleic acid for myristic acid was shown on the level of both a-linolenic and linoleic acids. Compared with the rats fed the diet containing no myristic acid, docosahexaenoic acid significantly increased in the brain and red blood cells of the rats fed the diet with 30% myristic acid and in the plasma of the rats fed the diet with 20% myristic acid. Arachidonic acid also increased in the brain of the rats fed the diet with 30% myristic acid. By measuring D6-desaturase activity, we found a significant increase in the liver of the rats fed the diet containing 10% of myristic acid but no effect at higher levels of myristic acid. These results suggest that an increase in dietary myristic acid may contribute in increasing significantly the tissue storage of a-linolenic acid and the overall bioavailability of (n-3) polyunsaturated fatty acids in the brain, red blood cells and plasma, and that mechanisms other than the single D6-desaturase activity are involved in this effect.

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Upregulated liver conversion of α-linolenic acid to docosahexaenoic acid in rats on a 15 week n-3 PUFA-deficient diet

Cited by 102 publications

References 68 publications

The metabolic syndrome of ω3-depleted rats. I. Liver data

The metabolic syndrome of ω3-depleted rats. I. Liver data

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

Substitution of dietary oleic acid for myristic acid increases the tissue storage of α-linolenic acid and the concentration of docosahexaenoic acid in the brain, red blood cells and plasma in the rat

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