FUEL HOMEOSTASIS AND CARNITINE METABOLISM IN RATS WITH SECONDARY BILIARY-CIRRHOSIS

Energy metabolism is abnormal in patients and experimental animals with liver cirrhosis. To help better understand the abnormalities, fuel homeostasis and carnitine metabolism were studied in fed and 24-hr-starved rats with secondary biliary cirrhosis induced by bile duct ligation for 4 wk. Plasma ketone body concentrations were decreased by 67% in starved, bile duct-ligated rats compared with control rats. In contrast, plasma nonesterified fatty acid concentrations were not different between bile duct-ligated and control rats in the fed or the fasted state. Plasma triglyceride concentrations showed the expected decrease with starvation in control rats, but were increased with starvation in bile duct-ligated rats. Urinary excretion of dicarboxylic acids was increased in both fed and fasted bile duct ligated-rats compared with the respective control groups. Compared with control rats, hepatic total carnitine content (per gram of liver) was increased by 24% in fed and by 36% in fasted, bile duct-ligated rats. Fed, bile duct-ligated rats had an increased short-chain acylcarnitine-to-carnitine ratio in liver, plasma and urine compared with control rats. Analysis of the hepatic coenzyme A pool showed decreased coenzyme A content in fed and fasted bile duct-ligated rats compared with control rats. Hepatic long-chain acylcarnitine and long-chain acyl-coenzyme A content increased with starvation both in control and bile duct-ligated rats. The rise in plasma nonesterified fatty acid concentration and hepatic long-chain acylcarnitine and long-chain acyl-coenzyme A contents with starvation in bile duct-ligated rats are consistent with unaltered hepatic availability of fatty acids. Thus bile duct-ligated rats demonstrated blunted ketosis during starvation and altered hepatic lipid metabolism. Bile duct-ligated rats represent an animal model for the study of fuel homeostasis and carnitine metabolism in the presence of chronic cholestatic liver disease.