The effect of methyl palmoxirate on incorporation of [U-14C]palmitate into rat brain.
We examined the dose response, time course and reversibility of the effect of methyl 2-tetradecylglycidate (McN-3716, methyl palmoxirate or MEP), an inhibitor of beta-oxidation of fatty acids, on incorporation of radiolabeled palmitic acid ([U-14C]PA) from plasma into brain lipids of awake rats. MEP (0.1, 1 and 10 mg/kg) or vehicle was administered intravenously from 10 min to 72 hr prior to infusion of [U-14C]PA. Two hr pretreatment with MEP (0.1 to 10 mg/kg) increased brain organic radioactivity 1.2 to 1.8 fold and decreased brain aqueous radioactivity by 1.2 to 3.0 fold when compared to control values. At 10 mg/kg, MEP significantly increased brain organic fraction from 40% in controls to 85%, 30 min to 6 hr pretreatment, and resulted in a redistribution of the radiolabeled fatty acid toward triacylglycerol. MEP changed the lipid/aqueous brain ratio of incorporated [U-14C]PA from 0.67 to 5.7. The incorporation rate coefficient, k*, was significantly increased by MEP (10 mg/kg) at 2 hr (31%), 4 hr (59%) and 6 hr (34%). All effects were reversed by 72 hr, consistent with a half-life of approximately 2 days for carnitine palmitoyl transferase I. These results indicate that intravenous MEP may be used with [1-11C]palmitic acid for studying brain lipid metabolism in vivo by positron emission tomography, as it significantly reduces the large unincorporated aqueous fraction that would result in high background radioactivity.
Chang
M C
MC
Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892.
Wakabayashi
S
S
Bell
J M
JM
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors; D004852:Epoxy Compounds / Q000494:pharmacology*; D007275:Injections, Intravenous; D050356:Lipid Metabolism; D008297:Male; D010168:Palmitates / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011916:Rats, Inbred F344
D002250:Carbon Radioisotopes; D004852:Epoxy Compounds; D010168:Palmitates; D011422:Propionates; D002334:Carnitine O-Palmitoyltransferase; C017522:methyl 2-tetradecylglycidate