Uptake and metabolism of plasma-derived erucic acid by rat brain |
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Authors: | Golovko Mikhail Y Murphy Eric J |
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Institution: | Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota, Grand Forks, ND 58202-9037, USA. |
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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. |
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Keywords: | arachidonic acid blood-brain barrier adrenoleukodystrophy fatty acid fatty acid uptake |
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