Submitted on January 18, 2006
Revised on April 4, 2006
Accepted on May 9, 2006
Rates of 
-linolenic acid incorporation into stable lipids and conversion to docosahexaenoic acid in liver of unanesthetized rats fed a high docosahexaenoate-containing diet
Miki Igarashi, Kaizong Ma, Lisa Chang, Jane M. Bell, Stanley I. Rapoport, and James C. DeMar . Jr
BPMS/NIA/NIH, Bethesda, MD 20892
Corresponding Author: mikii{at}mail.nih.gov
We quantified rates of incorporation of a-linolenic acid (a-LNA, 18:3n-3) into “stable” lipids (e.g. triacylglycerol, phospholipid, cholesteryl ester), as well as the rate of conversion of a-LNA to docosahexaenoic acid (DHA, 22:6n-3), in the liver of unanesthetized male rats on a diet whose fatty acid content contained 2.3% DHA (of total fatty acid, wt/wt). We infused [1-14C]a-LNA intravenously in these rats to produce a steady-state plasma radioactivity, collected arterial plasma, microwaved and removed the liver at 5 min, then measured specific activities of plasma and liver lipids. At 5 min, 72.7% of liver radioactivity (excluding unesterified fatty acid radioactivity) was in stable lipids, whereas the remainder was in the aqueous compartment (largely products of beta-oxidation). Taking into account the steady-state specific activity of the liver a-LNA-CoA precursor pool, in the form of the measured dilution coefficient, we used our in vivo model to calculate incorporation rates of unesterified a-LNA into liver triacylglycerol, phospholipid and cholesteryl ester (2401, 749 and 9.6 nmol/s/g x 10-4, respectively [sum = 3160 nmol/s/g x 10-4]), and a lower bound for the rate of synthesis of DHA from a-LNA by the liver, 15.8 nmol/s/g x 10-4 (0.5% of net incorporation rate). Turnover rates of a-LNA in liver triacylglycerol, phospholipid and cholesteryl ester equaled 3.2, 8.7 and 2.9 %/min, respectively, corresponding to half-lives of 8-24 min. Thus, in animals fed a high DHA-containing diet, rates of beta-oxidation and esterification of a-LNA into stable liver lipids are high, compared with a low rate of a-LNA conversion to DHA. Comparison with published brain data suggests that the conversion rate is insufficient to supply significant DHA to brain.High a-LNA incorporation and turnover rates likely reflect a high rate of secretion by liver of stable lipids packaged within very low density lipoproteins.
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