In vivo conversion of 18- and 20-C essential fatty acids in rats using the multiple simultaneous stable isotope method

Lin, Yu Hong; Salem, Norman

doi:10.1194/jlr.m500127-jlr200

Cited by 19 publications

(16 citation statements)

References 57 publications

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“…AA, which is mostly acquired from the diet or synthesized through elongation and desaturation of 18:2n6, is the major n6 LC-PUFA of the neural and vascular tissues of the retina and brain ( 22 ). Over the decades, much has been done showing that these LC-PUFAs are necessary for normal neural development and function (24)(25)(26)(27)(28)(29)(30)(31)(32). They also play signifi cant roles in maintaining cell structure and physiological function by modulating cell differentiation and normal growth through signal transduction and cellular metabolism (33)(34)(35).…”

mentioning

confidence: 99%

ELOVL4 protein preferentially elongates 20:5n3 to very long chain PUFAs over 20:4n6 and 22:6n3

Benham

Logan

et al. 2012

Journal of Lipid Research

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confidence: 99%

ELOVL4 protein preferentially elongates 20:5n3 to very long chain PUFAs over 20:4n6 and 22:6n3

Benham

Logan

et al. 2012

Journal of Lipid Research

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“…In the course of performing measurements of human (18) and rat (19) plasma samples containing multiple stable isotopes, it became apparent that there were several analytical difficulties. The plasma matrix exerted a suppressing effect on the fatty acid isotopic signals as measured in the NCI mode.…”

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confidence: 99%

Simultaneous quantitative determination of deuterium- and carbon-13-labeled essential fatty acids in rat plasma

Lin

Pawlosky

Salem

2005

Journal of Lipid Research

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This study reports methods for the quantitative determination of stable isotope-labeled essential fatty acids (EFAs) as well as an experiment in which deuterium-labeled linoleic acid (18:2n-6) and ␣ -linolenic acid (18:3n-3) were compared with those labeled with carbon-13 in rat plasma in vivo. Standard curves were constructed to compensate for concentration and plasma matrix effects. It was observed that endogenous pools of fatty acids had a greater suppressing effect on the measurements of 13 C-U-labeled EFAs relative to those labeled with 2 H 5 . Using these methods, the in vivo metabolism of orally administered deuterated-linolenate, 13 C-U-labeled linolenate, deuterated-linoleate, and 13 C-U-labeled linoleate was compared in adult rats (n ‫؍‬ 11). There were no significant differences in the concentrations of the 2 H versus 13 C isotopomers of 18:2n-6, 18:3n-3, arachidonic acid (20:4n-6), and docosahexaenoic acid (22:6n-3) in rat plasma samples at 24 h after dosing. Thus, there appears to be little isotope effect for 2 H 5 -versus 13 C-U-labeled EFAs when the data are calculated using the conventional standard curves and corrected for endogenous fatty acid pool size and matrix effects. In essential fatty acid (EFA) metabolic studies, 2 H and 13 C are the most commonly used stable isotopic atoms in tracer studies (1-6) since their discovery (7, 8) and application to metabolic studies about 70 years ago (9). Compared with 2 H, the 13 C atom has a relatively small difference in mass with respect to 12 C and so is very similar in its physicochemical characteristics. For 13 C-labeled fatty acids, a high-precision gas chromatography-combustion isotope ratio mass spectrometric system could detect 13 C in fatty acids at very low signal levels, down to 3 pmol per injection (10). 2 H-labeled fatty acids were used extensively and measured by GC-MS in electron impact (11), positive chemical ionization (12), and negative chemical ionization (NCI) (13) in biological samples. Other non-mass spectrometry methods, such as conventional GC with a flame ionization detector (FID), could be applied when the deuterated fatty acids had enough mass difference to be chromatographically resolved (13-15) and when sufficient amounts occurred in biological experiments such that they could be adequately detected (15-17). However, for fatty acids, no direct comparisons have been made between the metabolic behavior of 2 H and 13 C tracers either in vitro or in vivo.In the course of performing measurements of human (18) and rat (19) plasma samples containing multiple stable isotopes, it became apparent that there were several analytical difficulties. The plasma matrix exerted a suppressing effect on the fatty acid isotopic signals as measured in the NCI mode. This suppression was greater for the 13 C signals relative to those of the same fatty acid labeled with 2 H. Therefore, standard curves for the various fatty acid isotopes to be used were required. In addition, methods were required for estimating the responses of fatty acid m...

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“…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).…”

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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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In vivo conversion of 18- and 20-C essential fatty acids in rats using the multiple simultaneous stable isotope method

Cited by 19 publications

References 57 publications

ELOVL4 protein preferentially elongates 20:5n3 to very long chain PUFAs over 20:4n6 and 22:6n3

ELOVL4 protein preferentially elongates 20:5n3 to very long chain PUFAs over 20:4n6 and 22:6n3

Simultaneous quantitative determination of deuterium- and carbon-13-labeled essential fatty acids in rat plasma

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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