Effect of inhibition of beta-oxidation on incorporation of [U-14C]palmitate and [1-14C]arachidonate into brain lipids.
The purpose of the present study was to determine the effect of inhibiting the mitochondrial beta-oxidation of free fatty acids on the incorporation of radiolabeled free fatty acids into brain lipids. To this end, methyl 2-tetradecylglycidate (MEP), an irreversible inhibitor of carnitine palmitoyltransferase I, was given orally to male rats 2, 4, and 6 h prior to an intravenous infusion of the saturated fatty acid [U-14C]palmitic acid (PA) or the polyunsaturated fatty acid [1-14C]arachidonate (AA). With [U-14C]PA, MEP (10-25 mg/kg) increased brain organic radioactivity 2-fold and decreased brain aqueous radioactivity 3- to 5-fold relative to control values at all pretreatment times. The effect was due to prolongation of the plasma integral of [U-14C]PA due to peripheral inhibition of beta-oxidation, and to direct inhibition of beta-oxidation of the tracer within the brain. MEP had no effect on brain organic radioactivity after infusion of [1-14C]AA. Increasing the interval between MEP administration and [U-14C]PA infusion from 2 to 6 h resulted in a dramatic redistribution of [U-14C]PA within brain lipids. The percentage of radioactivity in phospholipids decreased from 65 to 33%, whereas that in the free fatty acid fraction increased from 10 to 47% and that in triglycerides was elevated 2-3 fold over control levels. These results indicate that MEP may facilitate the use of radiolabeled PA as an in vivo probe of brain lipid metabolism using quantitative autoradiography or positron emission tomography.
Freed
L M
LM
Laboratory of Neurosciences, NIA, NIH, Bethesda, MD 20892.
Wakabayashi
S
S
Bell
J M
JM
Rapoport
S I
SI
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000494:pharmacology; D005215:Fasting; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D002250:Carbon Radioisotopes; D004852:Epoxy Compounds; D008055:Lipids; D010169:Palmitic Acids; D011422:Propionates; D016718:Arachidonic Acid; D019308:Palmitic Acid; C017522:methyl 2-tetradecylglycidate