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Journal of Lipid Research, Vol. 47, 1812-1822, August 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Low liver conversion rate of -linolenic to docosahexaenoic acid in awake rats on a high-docosahexaenoate-containing diet

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

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

Published, JLR Papers in Press, May 10, 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, Rockville, MD 20892.

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

We quantified the rates of incorporation of -linolenic acid (-LNA; 18:3n-3) into "stable" lipids (triacylglycerol, phospholipid, cholesteryl ester) and the rate of conversion of -LNA to docosahexaenoic acid (DHA; 22: 6n-3) in the liver of awake male rats on a high-DHA-containing diet after a 5-min intravenous infusion of [1-¹⁴C]-LNA. At 5 min, 72.7% of liver radioactivity (excluding unesterified fatty acid radioactivity) was in stable lipids, with the remainder in the aqueous compartment. Using our measured specific activity of liver -LNA-CoA, in the form of the dilution coefficient _-LNA-CoA, we calculated incorporation rates of unesterified -LNA into liver triacylglycerol,phospholipid, and cholesteryl ester as 2,401, 749, and 9.6 nmol/s/g x 10^–4, respectively, corresponding to turnover rates of 3.2, 8.7, and 2.9%/min and half-lives of 8–24 min. A lower limit for the DHA synthesis rate from -LNA equaled 15.8 nmol/s/g x 10^–4 (0.5% of the net in corporation rate). Thus, in rats on a high-DHA-containing diet, rates of ß-oxidation and esterification of -LNA into stable liver lipids are high, whereas its conversion to DHA is comparatively low and insufficient to supply significant DHA to the brain. High incorporation and turnover rates likely reflect a high secretion rate by liver of stable lipids within very low density lipoproteins.

Supplementary key words incorporation • turnover • synthesis • pulse labeling • infusion • diet

Abbreviations: DHA, docosahexaenoic acid (22:6n-3); di-17:0 PC, di-heptadecanoate phosphatidylcholine; EPA, eicosapentaenoic acid (20:5n-3); FAME, fatty acid methyl ester; LA, linoleic acid (18:2n-6); -LNA, -linolenic acid (18:3n-3)

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