Time course of changes in hepatic metabolism in response to sepsis in the rat: Impairment of gluconeogenesis and ketogenesis in vitro

Abstract

1. The time course (12, 24 and 48 h) of changes in blood metabolites, and in gluconeogenesis and ketogenesis, in isolated hepatocytes from rats made septic by caecal ligation and puncture was measured. 2. Blood glucose was not significantly different in septic rats, but lactate was increased at 12, 24 and 48 h; pyruvate and alanine were increased at 48 h. The blood ketone body concentrations were decreased at all times studied after induction of sepsis. These changes were accompanied by increased plasma insulin in the septic rats. 3. The rate of hepatic lipogenesis in vivo was increased at 24 and 48 h. 4. There were appreciable increases in the hepatic concentrations of alanine (200%), lactate (200%) and pyruvate (100%) as well as other intermediates in the gluconeogenic pathway. The hepatic concentrations of acetyl-CoA and ketone bodies were decreased. 5. The rate of gluconeogenesis from added lactate, pyruvate, alanine and glutamine was depressed in isolated hepatocytes from septic rats at 24 and 48 h. 6. The basal rate of ketogenesis or the rate from butyrate in isolated hepatocytes was not significantly altered by sepsis, whereas the rate from oleate was decreased at all time points. 7. It is concluded that there is an impairment of the capacity for gluconeogenesis and ketogenesis in livers of septic rats. The latter may be due to decreased entry of long-chain acyl-CoA into the mitochondria for oxidation. The possibility that these changes are in part brought about by the hyperinsulinaemia associated with the sepsis is discussed.