Hepatic [2-¹³C]acetate metabolism by jirds infected with Echinococcus multilocularis

Abstract

Carbon-13 decoupled 1H spin echo NMR spectroscopy, with and without population inversion, was used to study carbon flow between the host, Meriones unguiculatus, and the parasite, Echinococcus multilocularis. This was accomplished by monitoring [2-13C]acetate metabolism in the liver of jirds infected with metacestodes of this parasite. Thirty minutes after injection of labelled acetate solution into the portal vein, 13C enrichment was observed in hepatic acetate, β–hydroxybutyrate, succinate, alanine, lactate and glucose. For E. multilocularis cysts, at this time,13C enrichment was observed in the same metabolites as in livers and, in addition, citrate. At 120 min there was a significant decrease in the amount of label present in all hepatic metabolites whereas more label was found in the majority of the parasite metabolites. The results confirm that exogenous acetate, through randomization of the 13C in biochemical pathways of host liver, ends up in hepatic glucose. As this biosynthetic route is not available to the parasite, the presence of 13C enriched glucose in the cysts clearly indicates that the parasite is siphoning off glucose that is newly synthesized by the host. At 120 min some of this labelled glucose was stored in parasite glycogen whereas some of it had been catabolized to succinate, alanine, lactate and acetate, end products which are excreted back into the host.

Effect of Echinococcus multilocularis on the origin of acetyl-CoA entering the tricarboxylic acid cycle in host liver

“…As pyruvate is produced by glycolysis and consumed by gluconeogenesis, parasite-induced starvation of the host should result in a depletion of hepatocellular pyruvate. That this is likely to have happened is further substantiated by evidence from previous research that gluconeogenesis is accelerated in hepatocytes of E. multilocularis-infected jirds (Schoen et al, 1999). The second reason why the cytosolic concentration of pyruvate is expected to be lower in infected animals has to do with the synthesis of ketone bodies.…”

“…The second reason why the cytosolic concentration of pyruvate is expected to be lower in infected animals has to do with the synthesis of ketone bodies. Ketogenesis is known to increase in livers of starving mammals (Seifter & Englard, 1994) and, more specifically, Schoen et al (1999) have provided evidence for accelerated ketogenesis in E. multilocularis-infected jirds. One of the ketone bodies, acetoacetate, is transported out of the mitochondrion in exchange for pyruvate (Kummel, 1987;Morand et al, 1993).…”

“…This glucose is derived from the breakdown of glycogen (glycogenolysis) or from de novo synthesis (gluconeogenesis) from lactate, alanine and other substrates (Van den Burghe, 1991;Seifter & Englard, 1994). Evidence for an increase in the rate of host gluconeogenesis in the E. multilocularis± M. unguiculatus system was provided by Schoen et al (1999) in a carbon-13 decoupled 1 H spin echo nuclear magnetic resonance (NMR) study of [2-13 C]acetate metabolism in the liver of the infected host. Also, the results confirmed that label from the exogenous acetate, through randomization of the 13 C in biochemical pathways of host liver, ends up in hepatic glucose and, more importantly for the study of host±parasite interaction, demonstrated that some of this newly synthesized glucose is taken up and utilized by the parasite.…”