Use of endogenous triglycerides to support gluconeogenesis in the perfused isolated rat liver

The carbon balances in isolated perfused rat liver during gluconeogenesis from L-alanine and sodium L-lactate indicate that assuming the substrate unaccounted for were fully oxidized the energy yielded was not sufficient to support the observed rates of glucose synthesis. This observation indicates that endogenous substrates must also be oxidized. The possibility that endogenous fatty acid oxidation was the source of the energy needed to support glucose synthesis was investigated by measuring the rate of 14CO2 formation from tracer quantities of added [U-14C] palmitate. Short pulses of L-alanine or sodium L-lactate infusion produced an increased rate of 14CO2 production paralleled by increases in oxygen uptake indicating that more endogenous fuel is being mobilized. That the rate of 14CO2 output is an expression of fatty acid mobilization was supported by experiments demonstrating that the addition of octanoate to dilute the fatty acid pool produced an immediate fall in the rate of 14CO2 output. On the other hand, the administration of glucose produced no changes in oxygen uptake or 14CO2 output. However, lactate even in the presence of glucose induced a rise in 14CO2 production which occurred in parallel with the enhancement in oxygen uptake. It is concluded that mobilization of hepatic endogenous fatty acid is a metabolic event intimately associated with enhancement of gluconeogenesis. Consequently the control of the different steps of this process may indirectly control gluconeogenesis.