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Papers In Press, published online ahead of print May 1, 2007
J. Lipid Res., doi:10.1194/jlr.M600549-JLR200

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Journal of Lipid Research, Vol. 48, 1150-1158, May 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Docosahexaenoic acid synthesis from -linolenic acid by rat brain is unaffected by dietary n-3 PUFA deprivation

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 a table.

Published, JLR Papers in Press, February 4, 2007.

² Present address of J. C. DeMar, Jr.: Laboratory of Membrane Biochemistry & 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

Rates of conversion of -linolenic acid (-LNA, 18:3n-3) to docosahexaenoic acid (DHA, 22:6n-3) by the mammalian brain and the brain's ability to upregulate these rates during dietary deprivation of n-3 polyunsaturated fatty acids (PUFAs) are unknown. To answer these questions, we measured conversion coefficients and rates in post-weaning rats fed an n-3 PUFA deficient (0.2% -LNA of total fatty acids, no DHA) or adequate (4.6% -LNA, no DHA) diet for 15 weeks. Unanesthetized rats in each group were infused intravenously with [1-¹⁴C]-LNA, and their arterial plasma and microwaved brains collected at 5 minutes were analyzed. The deficient compared with adequate diet reduced brain DHA by 37% and increased brain arachidonic (20:4n-6) and docosapentaenoic (22:5n-6) acids. Only 1% of plasma [1-¹⁴C]-LNA entering brain was converted to DHA with the adequate diet, and conversion coefficients of -LNA to DHA were unchanged by the deficient diet. In summary, the brain's ability to synthesize DHA from -LNA is very low and is not altered by n-3 PUFA deprivation. Because the liver's reported ability is much higher, and can be upregulated by the deficient diet, DHA converted by the liver from circulating LNA is the source of the brain's DHA when DHA is not in the diet.

Supplementary key words n-3 polyunsaturated fatty acid • diet • elongation • fatty acid • synthesis

Abbreviations: AA, arachidonic acid; DHA, docosahexaenoic acid; DPA, docosapentaenoic acid; EPA, eicosapentaenoic acid; FAME, fatty acid methyl ester; LA, linoleic acid; -LNA, -linolenic acid

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