Hepatic and Cerebral Energy Metabolism after Neonatal Canine Alimentation

Abstract

Summaryduration than older rats (13,14). In other investigations amongIntrahepatic and intracerebral metabolic responses to neonatal fasting or enteric carbohydrate alimentation were investigated among newborn dogs. Pups were either fasted or given an intravenous glucose infusion (alimented) before an enteric feeding of physiologic quantities of either glucose or galactose. These pups were also compared to another group which was completely starved throughout the study period. Gastrointestinal carbohydrate feeding resulted in enhanced hepatic glycogen content among pups after a prior state of fasting. Though there were no differences of glycogen content between glucose or galactose feeding in this previously fasted group, combined intravenous glucose and enteric galactose administration produced the greatest effect on hepatic glycogen synthesis. Intrahepatic fructose 1, 6-diphosphate and phosphoenolpyruvate levels were increased among previously fasted pups fed enteric monosaccharides compared to completely starved control pups, whereas intrahepatic phosphoenolpyruvate and pyruvate levels were elevated after combined intravenous and enteric carbohydrate administration. Of greater interest was the observation that hepatic levels of ATP were significantly elevated among all groups given exogenous carbohydrates compared to the completely starved control group. In contrast to the augmented hepatic glycogen and ATP levels, there were no alterations of cerebral glycogen or ATP after alirnentation. Nevertheless, cerebral pyruvate and/or phosphoenolpyruvate concentrations were elevated after enteric or combined intravenous and enteric alimentation compared to the totally starved control pups. newborn piglets, starvation was associated with a decreased b a d metabolism rate as evident by diminished rates of oxygen consumption (9).Past experience among human newborn infants has demonstrated that early alimentation prevents fasting hypoglycemia and improves neonatal survival (1, 6, 43). Additionally, alimentation of newborn rats results in stable blood glucose concentrations and glucose production rates and also augments circulating alternate fuels levels (1 1, 12).Rapid alterations of intrahepatic metabolic intermediates, cofactors, and regulatory enzymes are essential controlling events that permit the liver's transition from a glucose-producing organ during starvation to an organ capable of net carbohydrate uptake during alimentation (15,33,34,38). This change is essential for the control of blood glucose levels, and for the replenishment of hepatic glycogen stores. During carbohydrate alimentation pyruvate becomes the predominant source of acetyl-CoA for the tricarboxylic acid cycle and may result in enhanced ATP production. The transition from fasting hepatic intermediary metabolism to that of an alimented state has been well documented among adult mammals. As there are little in vivo data describing the regulation of intrahepatic metabolism among fasted neonates, or the response of the neonatal liver to subsequent al...

Sequential Intrahepatic Metabolic Effects of Enteric Galactose Alimentation in Newborn Rats

“…The alteration of glucosed-phosphate suggests that both carbohydrates enriched this intermediate pool (19,21). Glucose would do this directly after phosphorylation by glucokinase (7). Galactose was readily converted to glucose during these current experiments as evident by the rapid appearance of l4 C label from galactose into circulating glucose.…”

“…Previous studies in our laboratory have investigated the effects of enteric glucose and galactose alimentation on perturbations of hepatic glycolytic and Kreb cycle intermediates (7). Compared with completely fasted newborn dogs, both glucose and galactose resulted in increased concentrations of various hepatic metabolites.…”

“…Standard fluorometric assays were used to determine hepatic, UDP-glucose, galactose-1-phosphate, fructose-6-phosphate, fructose 1, 6 diphosphate, phosphoenolpyruvate, pyruvate, lactate, citrate, and ATP (7,9). Galactose-1-phosphate was determined because elevated levels are associated with toxicity in galactosemia.…”

“…In these investigations hepatic tissue sampling was delayed and occurred after completion of the kinetic studies. This delay was 3-4 h after the carbohydrate load (7). Blood levels of galactose were maximum 30 min after ingestion and returned to very low baseline levels within 90 min.…”

“…Our previous investigations of the metabolic differences between galactose and glucose studied glucose kinetics in addition to the metabolic pertubations in neonatal canine liver (7). Hepatic metabolic alterations include an equivalent increase in glycogen content after the administration of glucose and galactose.…”