Fetal and Neonatal Responses to Extended Maternal Canine Starvation. II. Fetal and Neonatal Liver Metabolism

SummaryThe effect of maternal starvation for 5 days on circulating fuels, on glucose, and on lactate turnover in fasted newborn dogs was studied at 0,3,6, 9, and 24 h of age. Maternal starvation reduced the birthweight of the puppies by 23% (232 + 6 versus 300 f 10 g).Fetal ketone body concentration (3.33 pnole/ml) paralleled the marked maternal hyperketonemia (5.78 pmole/ml).After birth, maternal canine starvation (MCS) also caused significantly lower fasting blood glucose values in the pups at 3 h of age compared to controls (2.79 versus 5.77 pmole/ml). In addition, plasma free fatty acids (FFA) and glycerol levels were significantly reduced at 3 h of age. At 6 h, glucose and FFA concentration became equivalent to controls. Glycerol concentration, however, remained depressed at 6 and 9 h, and plasma triglyceride levels were significantly elevated. A significant rise in blood alanine concentration was observed at 3,6, and 24 h of age in MCS pups. In spite of low blood glucose values at 3 h of age, the glucose production rate (GPR) in the MCS pups was the same as in the controls. Lactate turnover and its carbon incorporation into glucose did not show any significant differences between MCS and control pups at individual time points.These data suggest that during starvation the mother was unable to provide sufficient substrates for normal fetal growth. Maternal and fetal nutrient deficiencv mav have resulted also in decreased neonatal blood glucose leveis together with reduced lipolysis in the immediate newborn period. Circulating glucose, FFA, and glycerol concentrations reached control values during the remainder of the study. Diminished availability of FFA may have resulted in enhanced tissue clearance of glucose. When lipolysis increased and peripheral tissue had an alternate fuel, glucose clearance returned to control values. The precise mechanism for the diminished levels of circulating fuels among fasted pups after 5 days of maternal starvation was not directly evident from these investigations of circulating fuels and glucose or lactate turnover data. Abbreviation FFA, free fatty acids GPR, glucose production rate MCS, maternal canine starvation Maternal starvation has been shown to reduce fetal birthweight and cause a significant decrease in fetal blood glucose concentration and an increase in fetal ketone body levels in different mammalian species (1, 7,9,23).The effect of maternal starvation upon fasting neonatal metabolic adaptation to birth has been investigated in dogs after 3 days of maternal starvation (12,15). In these earlier studies maternal starvation caused a very small fetal weight loss and an increase in fetal blood ketone body levels. During the early hours of neonatal life, pups of these starved mothers had decreased fasting blood glucose and plasma FFA levels; at the same time glucose production rates were also attenuated. It was hypothesized that limited hepatic FFA oxidation may have delayed the activation of gluconeogenesis needed to enhance hepatic glucose production.As 3 days of mat...

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“…The effect of maternal starvation on intrahepatic intermediates was also evaluated. The results are reported in accompanying paper (16).…”

Section: Methodsmentioning

confidence: 69%

Fetal and Neonatal Responses to Extended Maternal Canine Starvation. I. Circulating Fuels and Glucose and Lactate Turnover

1983

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“…Cesarean section was done at term (60 + 2 days). The newborn pups were immediately transferred to an incubator maintained at 37" C with relative humidity of 70% (5,8). The newborn pups were fasted throughout the study period in both groups.…”

Section: Louis Momentioning

confidence: 99%

Cerebral Metabolic Intermediate Response following Severe Canine Intrauterine Growth Retardation

Kliegman

1986

Pediatr Res

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ABSTRACT. The effect of intrauterine growth retardation and neonatal hypoglycemia on cerebral metabolic intermediates were determined in newborn dogs subjected to 5 days of maternal canine starvation (MCS) before birth.Birth weight was reduced 23% (232 + 6 versus 300 f 10 g). Circulating blood glucose was reduced after 3 h of neonatal fasting in MCS pups (2.7 f 0.4 f versus 5.7 + 1.1 mM). Cerebral cortical levels of glucose were also reduced at this time. Cerebral glucose-6-phosphate was not altered; nonetheless fructose-6-phosphate was lower in MCS pups at 6 and 9 h, while fructose 1,6-diphosphate appeared elevated at 3 h. These data suggest that cerebral glycolytic activity may be increased by increased activity of phosphofructokinase. Cerebral glutamine appeared reduced in fasting MCS pups at 3, 6, and 8 h of age. A considerable disturbance of the adenine nucleotide pool was noted between 3-9 h in MCS pups; while the cerebral energy reserve was diminished in MCS pups between 3-24 h. The data of reduced cerebral energy status and reserve suggest that cerebral energy production was diminished. Although glucose levels were low at 3 h, subsequent recovery was not immediate as adenine-nucleotides remained low beyond the period of hypoglycemia. The combined effects of intrauterine growth retardation and transient neonatal hypoglycemia appear to result in reduced cerebral oxidative metabolism; this occurs despite an apparent enhanced utilization of alternate fuels. (Pediatr Res 20: 662-667,1986 uterine growth retardation is abnormal, and is characterized by fasting hypoglycemia, attenuated FFA levels, and increased plasma levels of gluconeogenic amino acids (3-5). Symptomatic fasting hypoglycemia may have adverse effects on the developing central nervous system (6). Hypoglycemia, combined with the adverse effects of intrauterine growth retardation, may seriously affect fetal brain growth and future brain function. Previous studies in our laboratory among mildly growth retarded newborn dogs demonstrated that the cerebral cortical metabolic state appeared unperturbed in the fetus at the time of birth (7). However, cerebral cortical metabolic changes in growth retarded newborn dogs were most marked with the development of fasting neonatal hypoglycemia after birth. Brain glucose and glycogen content and the calculated energy reserve were diminished during the 24-h period following birth. Nonetheless, cerebral ATP levels were unaltered. Cerebral amino acid patterns suggested that the glutamate group of amino acids were functioning as alternate fuels and were being oxidized to support brain energy metabolism.As 3 days of maternal nutritional deprivation only resulted in a small reduction of fetal growth, we have extended the period of nutritional deprivation to 5 days. This extended period of nutrient withdrawal has resulted in marked intrauterine growth retardation, and has produced circulating substrate perturbations which parallel those observed in the human growth-retarded infant (5). The present report concerns the e...

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“…Our results for ATP in normal neonatal dogs are not different from those values reported by others in newborn dogs and rodents (9, 10). Thereafter, glycogen, glucose, UDP glucose, glucose-6-phosphate, fructose-6-phosphate, phosphoenolpyruvate, pyruvate, and lactate were assayed as reported previously (2,8). Cerebral cytoplasmic NAD/NADH ratio was calculated as described before (2,8).…”

Section: Kliegmanmentioning

confidence: 99%

“…Thereafter, glycogen, glucose, UDP glucose, glucose-6-phosphate, fructose-6-phosphate, phosphoenolpyruvate, pyruvate, and lactate were assayed as reported previously (2,8). Cerebral cytoplasmic NAD/NADH ratio was calculated as described before (2,8). All analyses were performed in duplicate.…”

Section: Kliegmanmentioning

confidence: 99%

“…Lactate oxidation rather than release to the systemic circulation may maintain cerebral ATP production in growth-retarded hypoglycemic newborn dogs. Fasting neonatal hypoglycemia is a common manifestation of altered fuel metabolism among mammals with intrauterine growth retardation (1)(2)(3). Maternal nutritional deprivation results in fetal growth retardation and fasting hypoglycemia among newborn dogs (l,2).…”

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confidence: 99%

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Cerebral Metabolic Response to Neonatal Hypoglycemia in Growth-Retarded Dogs

Kliegman

1988

Pediatr Res

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ABSTRACT. The cerebral metabolic effects of hypoglycemia due to intrauterine growth retardation were studied in newborn dogs. Intrauterine growth retardation was induced in newborn dogs after 3 days of maternal nutritional deprivation (birth weight 251 f 7 versus 227 f 7 g, p < 0.01). After birth, growth retarded pups developed fasting neonatal hypoglycemia which lasted from 3 to 9 h of life. The cerebral arteriovenous differences for glucose, oxygen, and ketone bodies were not different between growthretarded pups or those from age-matched controls. The cerebral venous efflux of lactate was reduced, whereas the extraction of glucose (relative to blood glucose) was enhanced among growth-retarded pups. Cerebral glycogen content was lower in pups with growth retardation whereas phosphoenolpyruvate and pyruvate concentrations were augmented among growth-retarded pups. The latter may reflect a more oxidized cytoplasmic redox state but may also be due to diminished lactate efflux from the brain. Cerebral ATP content was not affected during periods of reduced blood glucose levels. These results suggest that in newborn dogs hypoglycemia associated with intrauterine growth retardation alters cerebral metabolism by increasing cerebral extraction of glucose and decreasing CNS efflux of lactate. We speculate that the net effect is increased lactate utilization within oxidative pathways and preservation of cerebral oxygen uptake. Cerebral glucose utilization is directed away from glycogen synthesis and toward glycolysis. Lactate oxidation rather than release to the systemic circulation may maintain cerebral ATP production in growth-retarded hypoglycemic newborn dogs. (Pediatr Res 24: 649-652,1988)

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Fetal and Neonatal Responses to Extended Maternal Canine Starvation. II. Fetal and Neonatal Liver Metabolism

Cited by 9 publications

References 18 publications

Fetal and Neonatal Responses to Extended Maternal Canine Starvation. I. Circulating Fuels and Glucose and Lactate Turnover

Fetal and Neonatal Responses to Extended Maternal Canine Starvation. I. Circulating Fuels and Glucose and Lactate Turnover

Cerebral Metabolic Intermediate Response following Severe Canine Intrauterine Growth Retardation

Cerebral Metabolic Response to Neonatal Hypoglycemia in Growth-Retarded Dogs

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