Ketone body-induced dissociation between hepatocyte gluconeogenesis and ureagenesis in acutely uremic rats

Ketone body production in isolated liver cells and the effect of ketone bodies on hepatocyte urea and glucose production were investigated in acutely uremic rats. Blood beta-hydroxybutyrate levels of starved acutely uremic rats were reduced compared to starved sham-operated controls, suggesting a failure to develop hyperketonemia. On the other hand, beta-hydroxybutyrate concentration is elevated in the liver. Hepatocyte beta-hydroxybutyrate production of acutely uremic animals is enhanced using serine as a substrate. Addition of ketone bodies abolishes this effect. Blood acetoacetate levels of starved acutely uremic rats are elevated compared to sham-operated controls. Liver acetoacetate concentration is unchanged in acute uremia. Hepatocyte acetoacetate production of acutely uremic rats is stimulated using serine and alanine as substrates. Again, this effect is reversed by addition of ketone bodies. Addition of ketone bodies does not affect enhanced glucose production from serine or alanine in hepatocytes of acutely uremic rats but decreases markedly enhanced urea production from serine (156 +/- 35.2 versus 27.4 +/- 7.1) and alanine (80.0 +/- 22.3 versus 42.0 +/- 4.4 nmol mg-1. 30 min-1), especially after bilateral nephrectomy. The data show that the two processes of gluconeogenesis and ureagenesis can be dissociated in hepatocytes of bilaterally nephrectomized rats by the addition of ketone bodies. The finding that ketone bodies decrease the rate of urea production may be worth further study.