ACYLCARNITINE FORMATION AND FATTY-ACID OXIDATION IN HEPATOCYTES FROM RATS TREATED WITH TETRADECYLTHIOACETIC ACID (A 3-THIA FATTY-ACID)

In livers of rats fed a single morning dose of 100 mg tetradecylthioac etic acid (TTA) total long-chain acyl-CoA increased significantly to 3 times control levels within 6 h, then the level declined almost to co ntrol value within the next morning. Hepatic malonyl-CoA was reduced 7 5% 6 h after TTA treatment. From 6 to 24 h malonyl-CoA increased about 10-fold to about 3 times that of controls. Paradoxically there was ne arly a 2-fold higher oxidation of both [1-C-14]palmitic acid (0.5 mM) and [1-C-14]oleic acid (0.5 mM) in hepatocytes isolated from rats 24 h after TTA treatment compared to controls. After 6 h, when malonyl-CoA was at a minimum in vivo, fatty acid oxidation in cells was not incre ased. Acylcarnitine formation in digitonin permeabilized hepatocytes i solated 24 h after administration of TTA was increased both in the abs ence and in the presence of malonyl-CoA. At 24 h peroxisomal palmitoyl -CoA oxidase activity was not increased. The results suggest that an i ncreased CPT activity and increased acylcarnitine formation in the pre sence of malonyl-CoA is a delayed response to increased acyl-CoA level s. Furthermore, in hepatocytes isolated after 24 h incorporation of [1 -C-14]oleic acid into triacylglycerols was significantly reduced. The data show that in hepatocytes isolated from rats 24 h after administra tion of a single dose of TTA, there is a diversion of hepatic acyl-CoA from synthesis of triacylglycerols into beta-oxidation in the mitocho ndria.