Fetal and neonatal responses to extended maternal canine starvation. II. Fetal and neonatal liver metabolism.

Abstract

Summary: The effects of maternal canine starvation (MCS) for 5 days on hepatic intermediates in fetus and fasted neonates were studied at 0, 3, 6, 9, and 24 h of age. Maternal starvation reduced the birth weights of the pups by 23% (232 ± 6 versus 300 ± 10 g). In the MCS fetuses, hepatic glycogen concentration was significantly decreased (416 versus 526 μmole/g) whereas uridine diphosphate glucose concentration was significantly increased (0.196 versus 0.135 μmole/g), suggesting diminished glycogen synthetase activity. After birth, hepatic glucose levels were significantly decreased at 3 (2.90 versus 5.95 μmole/g) and 24 (3.09 versus 5.29) h in the MCS pups. Glucose-6-phosphate (G6P) and fructose-6-phosphate (F6P) levels were low in MCS pups throughout the study, G6P being significantly decreased at 9 and 24 h, and F6P at 0, 6, 9, and 24 h in the MCS group. Fructose 1,6-diphosphate did not show any changes among groups. Of greater importance, hepatic ATP concentrations were significantly reduced in the MCS pups throughout the first day of life. Maternal fasting results in attenuated fetal hepatic glycogen synthesis and an altered transition from fetal to neonatal life. Diminished G6P and F6P levels suggest that hepatic glycolytic activity may be enhanced at the level of phosphofructokinase. In the presence of lactate carbon incorporation into glucose that approaches control rates of gluconeogenesis, the diminished G6P and F6P levels also suggest significant recycling of lactate carbon between glucose and lactate. Furthermore, despite the apparent predominance of glycolysis, diminished hepatic ATP levels suggest that MCS plus neonatal fasting produced a hepatic energy deficiency state. Hepatic substrate deficiency and altered energy production may result from the diversion of glycogen derived glucose to support systemic glucose production.