The liver carnitine pool reflects alterations in hepatic fatty acid metabolism in rats with bile duct ligation before and after biliodigestive anastomosis

Abstract

Background/Aims: Rats with long-term bile duct ligation (BDL rats) have impaired hepatic fatty acid metabolism and alterations in carnitine homeostasis. Analysis of the carnitine tissue and body fluid pools was used as a tool to study hepatic fatty acid metabolism in BDL rats and after reversal of bile duct ligation by Roux-en-Y anastomosis for 5 (RY5) or 14 days (RY14).Methods: Control rats were pair-fed to treated rats, and all rats were studied after starvation for 24 h. Carnitine was analyzed by a radioenzymatic method and by high performance liquid chromatography.Results: Both BDL and RY rats had decreased plasma β-hydroxybutyrate concentrations, whereas free fatty acid plasma concentrations were not different from control rats. Free carnitine plasma concentrations were not different between BDL or RY and control rats, whereas acetylcarnitine concentrations were decreased in BDL and RY rats, and showed a positive correlation with the plasma β-hydroxybutyrate concentrations. In comparison to control rats, the total hepatic carnitine content was increased in BDL and RY rats, both when expressed per g tissue and per total liver. This rise in the hepatic carnitine content was due to increases in both free and acylcarnitines, including acetylcarnitine. In comparison to control rats, the hepatic concentration of ß-hydroxybutyrate was decreased in BDL and RY rats, findings compatible with impaired formation of ketone bodies from acetyl-CoA. Urinary excretion of total carnitine was not different between treated and control rats.Conclusions: Hepatic metabolism of fatty acids is impaired in BDL rats and does not recover during the 14 days after Roux-en-Y anastomosis. The increased hepatic carnitine content in BDL and RY rats can best be explained by decreased export of carnitine from the hepatocytes. The alterations in the hepatic carnitine pool and impaired hepatic fatty acid metabolism in BDL and RY rats are compatible with impaired ketogenesis.