Effect of starvation on gene expression of regulatory enzymes of glycolysis/gluconeogenesis in genetically obese (fa/fa) Zucker rats

Abstract

OBJECTIVE: To study the mechanism that controls fructose-2,6-bisphosphate (Fru-2,6-P₂) accumulation, as well as the mRNAs levels of the glycolytic/gluconeogenic regulatory enzymes in the livers of fed and starved lean (fa/-) and obese (fa/fa) Zucker rats.

DESIGN: Rats were fed a standard chow or deprived of food for 24 h.

SUBJECTS: Male lean (fa/-) and genetically obese (fa/fa) rats (nine weeks old).

MEASUREMENTS: Fru-2,6-P₂ concentration, 6-phosphofructo-2-kinase (PFK-2), glucokinase (GK), pyruvate kinase (PK) activities and the mRNA levels of GK, PFK-2, L-type pyruvate kinase, fructose-1,6-bisphosphatase (FBPase-1) and phosphoenolpyruvate carboxykinase (PEPCK) were analyzed.

RESULTS: PFK-2/FBPase-2 mRNA decreased during starvation in both fa/- and fa/fa animals. Although PFK-2/FBPase-2 mRNA levels were similar in fed lean and obese rats, PFK-2 concentration and activity were higher in fed obese than in fed lean animals, which might explain the high concentration of Fru-2,6-P₂ observed in obese animals. During starvation, PFK-2 protein concentration decreased, correlating with the enzymatic activity and Fru-2,6-P₂ levels. The activities of GK and L-pyruvate kinase (L-PK) also increased in fed obese (fa/fa) rats compared with fed lean (fa/-) animals, but decreased during starvation. The mRNA levels of glycolytic enzymes in fed obese rats were similar (PFK-2) or higher than (GK, L-PK) in fed lean animals. During starvation, they decreased in lean and obese rats with one important exception, GK mRNA remained high in obese animals. The mRNA of gluconeogenic enzymes remained constant (FBPase-1) or increased (PEPCK) during fasting.

CONCLUSION: The changes observed might be explained by the hyperinsulinaemia observed in the liver of obese rats, which might lead to the stimulation of glycolysis and lipogenesis.