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A more recent version of this article appeared on January 1, 2007

Papers In Press, published online ahead of print October 18, 2006
J. Lipid Res., doi:10.1194/jlr.M600396-JLR200
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Submitted on September 5, 2006
Revised on October 17, 2006
Accepted on October 18, 2006

Liver conversion of alpha -linolenic acid to docosahexaenoic acid is upregulated in adult rats fed an n-3 PUFA deficient diet for 15 weeks

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

BPMS/NIA/NIH, Bethesda, MD 20892

Corresponding Author: mikii{at}mail.nih.gov

We quantified incorporation rates of plasma-derived alpha -linolenic acid (a-LNA, 18:3n-3) into “stable1 liver lipids (triacylglycerol, phospholipid and cholesteryl ester), and the rate of conversion of alpha -LNA to docosahexaenoic acid (DHA, 22:6n-3), in male rats fed, after weaning, an n-3 polyunsaturated fatty acid (PUFA) adequate diet (4.6% alpha -LNA, no DHA) or deficient diet (0.2% alpha -LNA, no DHA) for 15 weeks. Unanesthetized rats were infused intravenously with [1-14C]alpha -LNA to rapidly produce a steady-state plasma radioactivity, arterial plasma was collected, and the liver was microwaved and removed at 5 min for analysis. Unlabeled plasma alpha -LNA and DHA concentrations in plasma and liver were reduced by > 90% in rats on the deficient diet, whereas unlabeled arachidonic acid (20:4n-6) and docosapentaenoic acid (22:5n-6) concentrations were increased significantly. Deprivation did not significantly change incorporation coefficients of alpha -LNA into stable liver lipids, but increased synthesis-incorporation coefficients of DHA from alpha -LNA by 6.6, 8.4 and 2.3 fold in triacylglycerol, phospholipid and cholesteryl ester, respectively. Assuming that synthesized-incorporated DHA eventually would be secreted within lipoproteins, we calculated liver DHA secretion rates of 2.19 and 0.82 mu mol/day in the n-3 PUFA adequate and deprived rats, respectively. The estimated liver DHA secretion rates exceed published rates of unesterified DHA consumption by brain by 6 and 10 fold, respectively, in the diet adequate and deprived rats, and should be sufficient to maintain normal and reduced brain DHA concentrations, respectively, in the two dietary conditions.


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