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Journal of Lipid Research, Vol. 47, 1289-1297, June 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Uptake and metabolism of plasma-derived erucic acid by rat brain

Mikhail Y. Golovko^* and Eric J. Murphy^1,*,

^* Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota, Grand Forks, ND 58202-9037
Department of Chemistry, University of North Dakota, Grand Forks, ND 58202-9037

Published, JLR Papers in Press, March 8, 2006.

¹ To whom correspondence should be addressed. e-mail: emurphy{at}medicine.nodak.edu

We examined the ability of erucic acid (22:1n-9) to cross the blood-brain barrier (BBB) by infusing [14–¹⁴C]22:1n-9 (170 µCi/kg, iv and icv) into awake, male rats. [1-¹⁴C]arachidonic acid (20:4n-6) [intravenous (i.v.)] was the positive control. After i.v. infusion, 0.011% of the plasma [14-¹⁴C]22:1n-9 was extracted by the brain, compared with 0.055% of the plasma [1-¹⁴C]20:4n-6. The [14-¹⁴C]22:1n-9 was extensively ß-oxidized (60%), compared with 30% for [1-¹⁴C]20:4n-6. Although 20:4n-6 was targeted primarily to phospholipid pools, 22:1n-9 was targeted to cholesteryl esters, triglycerides, and phospholipids. When [14-¹⁴C]22:1n-9 was infused directly into the fourth ventricle of the brain [intracerebroventricular (i.c.v.)] for 7 days, 60% of the tracer entered the phospholipid pools, similar to the distribution observed for [1-¹⁴C]20:4n-6. This demonstrates plasticity in the ability of the brain to esterify 22:1n-9 in an exposure-dependent manner. In i.v. and i.c.v. infused rats, a significant amount of tracer found in the phospholipid pools underwent sequential rounds of chain shortening and was found as [12-¹⁴C]20:1n-9 and [10-¹⁴C]oleic acid. These results demonstrate for the first time that intact 22:1n-9 crosses the BBB, is incorporated into specific lipid pools, and is chain-shortened.

Supplementary key words arachidonic acid • blood-brain barrier • adrenoleukodystrophy • fatty acid • fatty acid uptake

Abbreviations: 18:1n-9, oleic acid; 20:4n-6, arachidonic acid; 22:1n-9, erucic acid; 24:0, lignoceric acid; 26:0, hexacosanoic acid; ALDP, adrenoleukodystrophy protein; BBB, blood-brain barrier; i.c.v., intracerebroventricular; i.v., intravenous; LO, Lorenzo's Oil; VLCFA, very long-chain saturated fatty acid; X-ALD, X-linked adrenoleukodystrophy

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