Inhibition of carnitine-acyl transferase I by oxfenicine studied in vivo with [ 11C]-labeled fatty acids

Abstract

Methods Anesthetized pigs were studied with [ 11C]-labeled fatty acids (FAs) with carbon chain length ranging from 8 to 16 carbon atoms, during control conditions and during inhibition of carnitine-palmitoyl transferase I (CPT I) with oxfenicine. The myocardial uptake of [ 11C]-FAs from blood was measured together with the relative distribution of [ 11C]-acyl-CoA between rapid mitochondrial oxidation and incorporation into slow turnover lipid pools in the heart. Results During baseline conditions, the fractional oxidative utilization of palmitate was almost as high as that of carnitine-independent short-chain FAs, unless the carnitine shuttle was inhibited by high levels of lactate. Inhibition of CPT I almost completely blocked the oxidative pathway for palmitic acid and reduced the fractional oxidative utilization, while the rate of oxidative metabolism of acyl-CoA was unaffected. Conclusions [ 11C]-Labeled FAs allow rapid oxidation to be well separated from esterification into slow turnover lipid pools in the heart of anaesthetized pigs. The fractional oxidative utilization of [ 11C]-palmitate serves well to characterize, in vivo, the carnitine-dependent transfer of long-chain FAs.