INCORPORATION OF [U-C-14]PALMITATE INTO RAT-BRAIN - EFFECT OF AN INHIBITOR OF BETA-OXIDATION

We examined the effect of a clinically therapeutic dose of methyl 2-te tradecylglycidate (McN-3716, methyl palmoxirate, MEP) (2.5 mg/kg), an inhibitor of beta-oxidation of fatty acids, on incorporation of radiol abeled palmitic acid ([U-C-14]PAM) from plasma into brain lipids of aw ake rats. Four hour pretreatment with 2.5 mg/kg MEP significantly incr eased the incorporation of [U-C-14]PAM into brain lipids and substanti ally decreased aqueous radiolabeled metabolites in brain that can cons titute unwanted background signal when analyzed by quantitative autora diography. MEP treatment increased the lipid to aqueous background rad ioactivity from 0.8 to 3.0. Net rate of incorporation, k, was signifi cantly increased (60%) by MEP and was attributed to incorporation of [ U-C-14]PAM into phospholipid and triglyceride brain compartments. MEP treatment did not affect the size of the fatty acyl-CoA pool or the di stribution of the Various molecular acyl-CoA species. These results in dicate that MEP, at a dose of 2.5 mg/kg (per os), can be used to incre ase incorporation of [1-C-11]PAM for studying brain lipid metabolism i n humans by positron emission tomography (PET).