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Effect of maternal protein deprivation during pregnancy on hepatic gluconeogenic enzyme in rat fetuses at term

Presented at the Neonatal Society 2004 Summer Meeting (programme).

Franko KL, Keele S, Forhead AJ, Fowden AL

Department of Physiology, University of Cambridge, Downing Street, Cambridge, CB2 3EG

Background: In rats, protein deprivation during pregnancy alters hepatic glucose handling in the adult offspring (1). In part, this is due to changes in the hepatic activity of enzymes involved in glucose metabolism although the extent to which these changes arise in utero or develop later in life remains unknown (1). In sheep, maternal undernutrition during late gestation is known to increase gluconeogenic enzyme activities in the fetal liver (2). This study examined the effect of feeding rats a low protein (LP) diet throughout pregnancy on fetal hepatic activities of the key rate-limiting enzymes in the glucogenic pathways, glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK).

Methods: Immediately after mating (0.5 days), female Wistar rats were fed ad libitum with either normal chow (20% protein, n = 7) or a low protein isocalorific diet (8% protein, n = 6) until 20.5 days of gestation (term 21 days) when their fetuses (LP, n = 93; Normal, n = 88) were delivered for tissue collection under terminal anaesthesia. After cerebral freezing, fetuses and placentae were weighed and fetal livers were frozen in liquid nitrogen for determination of G6Pase and PEPCK activities as described previously (3). Data is presented as mean ( SE) of the litter means for each animal.

Results: Maternal protein deprivation significantly decreased fetal and placental weights but significantly increased the fetal to placental weight ratio compared to normally fed animals (Table 1). Fetuses of LP mothers also had significantly higher hepatic activities of G6Pase, but not PEPCK, than those of normal mothers (Table 1). There was no significant difference in hepatic protein content between fetuses of LP (91.6 2.7 mg/g, n = 6) or normal mothers (94.2 2.4 mg/g, n = 7, P>0.05). Litter size did not vary significantly with dietary treatment.

Table 1. Morphometry and hepatic gluconeogenic enzymes activities of rat fetuses from mothers on LP or normal diets throughout pregnancy* significantly different from values in the normal animals, P<0.02 (unpaired t-test).

Conclusions: The results show that maternal protein deprivation increases placental efficiency and the activity of G6Pase in fetal rat liver. Hence, the abnormalities in glucose metabolism observed previously in the adult offspring of LP mothers may track from fetal life.

1. Ozanne, S (2001). BMB 60 143-152.
2. Lemons, J. et al., (1986). Ped. Res. 20 676-679
3. Fowden, A.L. et al., (1993) J. Endo. 137 213-222.

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