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Papers In Press, published online ahead of print January 1, 2007
J. Lipid Res., doi:10.1194/jlr.M600396-JLR200

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Journal of Lipid Research, Vol. 48, 152-164, January 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

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

Miki Igarashi¹, James C. DeMar, Jr.², Kaizong Ma, Lisa Chang, Jane M. Bell and Stanley I. Rapoport

Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of three tables.

Published, JLR Papers in Press, October 18, 2006.

² Present address of J. C. DeMar, Jr.: Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Bethesda, MD 20892.

¹ To whom correspondence should be addressed. e-mail: mikii{at}mail.nih.gov

We quantified incorporation rates of plasma-derived -linolenic acid (-LNA, 18:3n-3) into "stable" liver lipids and the conversion rate of -LNA to docosahexaenoic acid (DHA, 22:6n-3) in male rats fed, after weaning, an n-3 PUFA-adequate diet (4.6% -LNA, no DHA) or an n-3 PUFA-deficient diet (0.2% -LNA, no DHA) for 15 weeks. Unanesthetized rats were infused intravenously with [1-¹⁴C]-LNA, and arterial plasma was sampled until the liver was microwaved at 5 min. Unlabeled -LNA and DHA concentrations in arterial plasma and liver were reduced >90% by deprivation, whereas unlabeled arachidonic acid (20:4n-6) and docosapentaenoic acid (22:5n-6) concentrations were increased. Deprivation did not change -LNA incorporation coefficients into stable liver lipids but increased synthesis-incorporation coefficients of DHA from -LNA by 6.6-, 8.4-, and 2.3-fold in triacylglycerol, phospholipid, and cholesteryl ester, repectively. Assuming that synthesized-incorporated DHA even tually would be secreted within lipoproteins, calculated liver DHA secretion rates equaled 2.19 and 0.82 µmol/day in the n-3 PUFA-adequate and -deprived rats, respectively. These rates exceed the published rates of brain DHA consumption by 6- and 10-fold, respectively, and should be sufficient to maintain normal and reduced brain DHA concentrations, respectively, in the two dietary conditions.

Supplementary key words deprivation • incorporation • turnover • synthesis • pulse labeling • diet • brain • polyunsaturated fatty acid

Abbreviations: AA, arachidonic acid (20:4n-6); DHA, docosahexaenoic acid (22:6n-3); DPA, docosapentaenoic acid (22:5); EPA, eicosapentaenoic acid (20:5n-3); FAME, fatty acid methyl ester; LA, linoleic acid (18:2n-6); -LNA, -linolenic acid (18:3n-3); UV, ultraviolet

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