Abstract
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 microCi/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 beta-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.
Highlights
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 mCi/kg, iv and icv) into awake, male rats. [1-14C]arachidonic acid (20:4n-6) [intravenous (i.v.)] was the positive control
In addition to mutations in Abcd1, expression of Abcd4 and Bg1, genes encoding for a peroxisomal membrane transporter protein and a VLCFA acyl-CoA synthetase, respectively, is reduced in normal white matter from X-ALD patients and Abbreviations: 18:1n-9, oleic acid; 20:4n-6, arachidonic acid; 22:1n9, 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 longchain saturated fatty acid; X-ALD, X-linked adrenoleukodystrophy
Because the [14-14C]22:1n9 was minimally metabolized into other n-9 family fatty acids, it is unlikely that the 18:0 represents recycled carbon, especially with only 0.3% in palmitic acid; rather, it more likely represents a contaminant in the customsynthesized tracer
Summary
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 mCi/kg, iv and icv) into awake, male rats. [1-14C]arachidonic acid (20:4n-6) [intravenous (i.v.)] was the positive control. 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.—Golovko, M. In addition to mutations in Abcd, expression of Abcd and Bg1, genes encoding for a peroxisomal membrane transporter protein and a VLCFA acyl-CoA synthetase, respectively, is reduced in normal white matter from X-ALD patients and Abbreviations: 18:1n-9, oleic acid; 20:4n-6, arachidonic acid; 22:1n9, 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 longchain saturated fatty acid; X-ALD, X-linked adrenoleukodystrophy. This article is available online at http://www.jlr.org
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