Gluconeogenesis in the livers of diet-restricted rats--a 13C nuclear magnetic resonance study

Gluconeogenic activity is reduced during starvation. However, it is less clear whether the utilization of gluconeogenic substrates is diminished with mild but prolonged diet restriction and, if so, whether there are intrinsic changes in the gluconeogenic pathway. We examined gluconeogenesis in the livers of diet-restricted rats with 13C nuclear magnetic resonance (NMR) spectroscopy.

Fischer 344 rats were given 88% (DR group) of what was consumed by the weight-matched ad libitum-fed normal rats (CL group). At the end of 5 weeks, the removed livers were perfused with [3-13C] alanine while 13C NMR spectroscopy was performed.

The final body and liver weights were the same for the two groups. In DR rats, both intrahepatic [3-13C] alanine and metabolites generated via pyruvate and oxaloacetate, including aspartate and carbamoyl aspartate, appeared in significantly reduced amounts. There was also marked diminution in the production of glucose.

In the livers of DR rats, alanine uptake through System A transport, the fluxes through pyruvate carboxylase, the biosynthesis of pyrimidine nucleotides, and the production of glucose from alanine were all significantly decreased with mild intake restriction. Attenuated protein synthesis in the liver of diet-restricted animals may be the cause for this decreased utilization of alanine for gluconeogenesis.