Abstract
We quantified the rates of incorporation of alpha-linolenic acid (alpha-LNA; 18:3n-3) into "stable" lipids (triacylglycerol, phospholipid, cholesteryl ester) and the rate of conversion of alpha-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-(14)C]alpha-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 alpha-LNA-CoA, in the form of the dilution coefficient lambda(alpha-LNA-CoA), we calculated incorporation rates of unesterified alpha-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 alpha-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 beta-oxidation and esterification of alpha-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.
Highlights
We quantified the rates of incorporation of alinolenic acid (a-LNA; 18:3n-3) into ‘‘stable’’ lipids and the rate of conversion of a-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]a-LNA
We did not examine the rate of DHA synthesis from a-LNA in the liver of these rats, nor did we explore the kinetics of other pathways of liver a-LNA metabolism
We reported that plasma specific activity had reached a steady state by 0.5 min into the [1-14C]a-LNA infusion period and that plasma triacylglycerol, phospholipid, and cholesteryl ester contained traces (0.95, 0.52, and 0.076%, respectively) of total plasma radioactivity at 5 min, whereas the unesterified fatty acid fraction contained 97%
Summary
We quantified the rates of incorporation of alinolenic acid (a-LNA; 18:3n-3) into ‘‘stable’’ lipids (triacylglycerol, phospholipid, cholesteryl ester) and the rate of conversion of a-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]a-LNA. A number of experimental procedures have been used to examine hepatic a-LNA metabolism, including studying isolated hepatocytes [8], infusing the liver in situ [9], and injecting labeled a-LNA intravenously in an animal and measuring its distribution in different liver compartments [10] None of these studies measured the specific activity of liver a-LNA-CoA, the precursor pool for a-LNA esterification into stable lipids and for steps of DHA synthesis. This prevented calculating exact incorporation and syn-.
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