The Effect of Insulin on the Intracellular Distribution of 14(R,S)-[18F]Fluoro-6-thia-heptadecanoic Acid in Rats

Purpose The aim of this study was to determine the effect of hyperinsulinemia on myocardial and hepatic distribution and metabolism of 14(R,S)-¹⁸F]fluoro-6-thia-heptadecanoic acid (¹⁸F]FTHA).Procedures Mitochondrial retention and intracellular lipid incorporation of ¹⁸F]FTHA were compared to that of ¹⁴C]-2-bromopalmitate or ¹⁴C]palmitate during hyperinsulinemic clamp vs. saline infusion in male Wistar rats.Results Mitochondrial ¹⁸F activity was increased in the heart (1.7 ± 0.4 vs. 0.5 ± 0.1% ID/g, P < 0.05), whereas it was reduced in the liver (1.1 ± 0.3 vs. 1.8 ± 0.4% ID/g, P < 0.05) during insulin vs. saline infusion, respectively. Mitochondrial ¹⁴C]-2-bromopalmitate activity was affected by insulin in a similar way in both tissues. The fractional esterification of ¹⁸F]FTHA into triglycerides was impaired compared to ¹⁴C]palmitate in both tissues, and ¹⁸F]FTHA was insensitive to the shift of esterification of fatty acids into complex lipids in response to insulin.Conclusions ¹⁸F]FTHA is sensitive to insulin-induced modifications of free fatty acid oxidative metabolism in rats but is insensitive to changes in nonoxidative fatty acid metabolism.