Regulation of ammonia-metabolizing enzymes expression in the liver of obese rats: differences between genetic and nutritional obesities.

Objective: To determine the expression of carbamoylphosphate synthetase (CPS) and glutamine synthetase (GS) in two different models of obese rats: genetically obese rats and diet obese rats.

Subjects: Lean and genetically obese (fa/fa) Zucker rats were used.

Design: Lean animals (30-60 d old) were fed for 30 d with standard chow pellets or with a hypercaloric cafeteria diet. Genetically obese rats were fed with standard chow pellets.

Measurements: Enzyme activity, protein (Western blot) and mRNA (Northern blot) contents of CPS and GS were measured in liver homogenates.

Results: In genetically obese animals CPS mRNA content was higher, and GS mRNA content was lower than in control animals; CPS protein content did not change and CPS activity was lower than in control rats. Diet-obese rats had higher levels of CPS and GS mRNAs than control animals; GS protein content and activity was higher than in the control group and at the same time, CPS activity was very low.

Conclusions: In the genetically obese animals the expression of CPS and GS is mainly regulated at the pre-translational level, whereas in the diet obese rats there is a noticeable post-translational component. A reciprocal regulation between CPS and GS can be established at pre-translational levels, whereas at post-transcriptional levels it cannot. It can be concluded that in diet-obese animals the mechanisms involved in retaining nitrogen (low CPS activity) are modulated at the post-translational level.