Incorporation of [U-14C]palmitate into rat brain: effect of an inhibitor of beta-oxidation.
We examined the effect of a clinically therapeutic dose of methyl 2-tetradecylglycidate (McN-3716, methyl palmoxirate, MEP) (2.5 mg/kg), an inhibitor of beta-oxidation of fatty acids, on incorporation of radiolabeled palmitic acid ([U-14C]PAM) from plasma into brain lipids of awake rats. Four hour pretreatment with 2.5 mg/kg MEP significantly increased the incorporation of [U-14C]PAM into brain lipids and substantially decreased aqueous radiolabeled metabolites in brain that can constitute unwanted background signal when analyzed by quantitative autoradiography. MEP treatment increased the lipid to aqueous background radioactivity from 0.8 to 3.0. Net rate of incorporation, k*, was significantly increased (60%) by MEP and was attributed to incorporation of [U-14C]PAM into phospholipid and triglyceride brain compartments. MEP treatment did not affect the size of the fatty acyl-CoA pool or the distribution of the various molecular acyl-CoA species. These results indicate that MEP, at a dose of 2.5 mg/kg (per os), can be used to increase incorporation of [1-(11C)]PAM for studying brain lipid metabolism in humans by positron emission tomography (PET).
Chang
M C
MC
Laboratory of Neurosciences, National Institutes on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Grange
E
E
Rabin
O
O
Bell
J M
JM
D000214:Acyl Coenzyme A / Q000096:biosynthesis* / Q000145:classification / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D004852:Epoxy Compounds / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism; D008055:Lipids / Q000145:classification; D008297:Male; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000032:analysis / Q000378:metabolism*; D010743:Phospholipids / Q000096:biosynthesis / Q000145:classification; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
D000214:Acyl Coenzyme A; D002250:Carbon Radioisotopes; D004852:Epoxy Compounds; D007004:Hypoglycemic Agents; D008055:Lipids; D010743:Phospholipids; D011422:Propionates; D019308:Palmitic Acid; C017522:methyl 2-tetradecylglycidate