PROGRAMMING OF HEPATIC INSULIN-SENSITIVE ENZYMES IN OFFSPRING OF RAT DAMS FED A PROTEIN-RESTRICTED DIET

Hepatic enzymes associated with glucose hemostasis were studied in off spring of dams fed either a 20% protein (control) or an isocaloric 8% protein (low-protein) diet during pregnancy and lactation. Additionall y, offspring were exposed to maternal 8% protein diet only during gest ation (recuperated) or lactation (postnatal low-protein). Glucokinase activity decreased (similar to 50%), whereas phosphoenolpyruvate carbo xykinase (PEPCK) activity increased (similar to 100%), in the low-prot ein and recuperated offspring compared with controls (P < 0.001) at 21 days of age. However, the postnatal low-protein offspring had enzyme activities comparable with those of controls. These changes were still evident in 11-mo-old offspring weaned onto a normal laboratory chow. Parallel changes were apparent in mRNA levels of glucokinase and PEPCK in the low-protein male offspring. Thus the effect of programming met abolism extends not only to protein biochemistry but possibly also to the regulation of gene expression. Furthermore, these changes could no t be attributed to glucagon or insulin, because ratios of these hormon es were comparable between the control and low-protein groups.