Erucic Acid is Differentially Taken up and Metabolized in Rat Liver and Heart

Abstract

Because X-linked adrenoleukodystrophy is treated using erucic acid (22:1n-9), we assessed its metabolism in rat liver and heart following infusion of [14-(14)C]22:1n-9 (170 Ci/kg) under steady-state-like conditions. In liver, 2.3-fold more tracer was taken up as compared to heart, accounted entirely by increased incorporation into the organic fraction (4.2-fold). The amount of tracer entering the aqueous fraction, which represents beta-oxidation, was not different between groups; however a significantly elevated proportion of tracer was in the heart aqueous fraction. In both tissues, 76% of the radioactivity found in the organic fraction was esterified in neutral lipids, while only about 10% was found esterified into phospholipids. In liver, 56% of lipid radioactivity was found in cholesteryl esters, whereas in heart 64% was found in triacylglycerols. Because 22:1n-9 can be chain shortened, we assessed tracer metabolism using phenacyl fatty acid derivatives esterified from saponified esterified neutral lipid (triacylglycerol/cholesteryl ester) and phospholipid fractions. In heart esterified neutral lipids, 75% of tracer was recovered as 22:1n-9 and only 10% as oleic acid (18:1n-9), while in liver only 25% of the tracer was recovered as 22:1n-9, while 50% was found as stearic acid (18:0) and 10% as 18:1n-9. In liver and heart phospholipids, the tracer was distributed amongst the n-9 fatty acid family. Thus, 22:1n-9 under went tissue selective metabolism, with conversion to 18:0 the dominant pathway in the liver presumably for export in the neutral lipids, while in heart it was found primarily as 22:1n-9 in neutral lipids and used for beta-oxidation.