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Sequential intrahepatic metabolic effects of enteric galactose alimentation in newborn rats
1Department of Pediatrics, Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106.
Insights
Newborn rats show faster hepatic glycogen synthesis after galactose compared to glucose feeding. Galactose may utilize a more direct pathway for neonatal glycogen synthesis, bypassing initial glucose metabolism.
Area of Science:
- Neonatal metabolism
- Carbohydrate metabolism
- Biochemistry
Background:
- Newborns have unique metabolic needs.
- Understanding substrate utilization is crucial for neonatal nutrition.
- Galactose and glucose metabolism pathways differ.
Purpose of the Study:
- To compare metabolic responses to enteric galactose versus glucose feeding in fasted newborn rats.
- To investigate the kinetics of hepatic glycogen synthesis after galactose and glucose administration.
- To explore the pathway of galactose conversion to glucose and its incorporation into glycogen.
Main Methods:
- Fasted 5- to 7-day-old newborn rats were fed enterically with galactose or glucose.
- Metabolic responses, including glycemic and insulinemic profiles, were measured.
- 14C-labeled substrates were used to trace metabolic pathways.
- Hepatic glycogen content and radioactivity were determined at various time points.
- Key hepatic metabolites, including galactose-1-phosphate and ATP, were analyzed.
Main Results:
- Galactose feeding resulted in attenuated glycemic and insulin responses compared to glucose.
- Hepatic glycogen synthesis was significantly more rapid and pronounced after galactose than glucose.
- 14C-label appeared in blood glucose within 15 minutes of galactose feeding, indicating rapid conversion.
- Hepatic glycogen showed higher 14C-radioactivity in galactose-fed pups.
- Elevated galactose-1-phosphate levels and a transient ATP decline were observed post-galactose feeding.
Conclusions:
- Hepatic glycogen synthesis is more rapid and initiated earlier with galactose than glucose in fasted newborn rats.
- Galactose may utilize a more direct pathway for neonatal hepatic glycogen synthesis.
- Glucose metabolism for glycogen synthesis appears less direct, potentially requiring further processing.
Abstract:
We determined metabolic responses after enteric galactose alimentation in 5- to 7-day-old newborn rats fasted for 24 h. The glycemic response was attenuated after enteric galactose feeding compared with the response after enteric glucose-fed rat pups. 14C radioactivity in blood from galactose-fed pups was reduced as counts in blood galactose were lower than counts in blood glucose in glucose-fed pups. Nonetheless within 15 min, [14C] from galactose appeared in blood glucose suggesting rapid conversion of galactose to glucose. The plasma insulin response was also attenuated after galactose feeding compared with the insulin response after enteric glucose. Hepatic glycogen content increased rapidly after enteric galactose feeding and was higher than after glucose feeding at 60, 120, and 180 min. Significant glycogen synthesis after oral glucose was delayed and occurred at 240 min. Carbon radioactivity in glycogen was higher in galactose fed pups between 15 and 360 min of the study. Serial determination of hepatic metabolites revealed an increase of galactose-1-phosphate levels after oral galactose at 240 and 300 min and a transient decline of ATP at 15 min. Other hepatic metabolites did not demonstrate significant differences between the two groups. These data suggest that hepatic glycogen synthesis is more rapid and occurs sooner after galactose than after glucose alimentation in previously fasted newborn rats. Galactose may enter a more direct pathway for neonatal hepatic glycogen synthesis. The relatively delayed entry of glucose label into hepatic glycogen and the delay of net glycogen synthesis after oral glucose suggest that glucose entry is not direct and may require further metabolism before incorporation into glycogen.(ABSTRACT TRUNCATED AT 250 WORDS)