Alterations of fasting glucose and fat metabolism in intrauterine growth-retarded newborn dogs.
Maternal nutritional deprivation resulted in reduced fetal weight at term gestation (251 +/- 7 vs. 277 +/- 7 g, P less than 0.01) in newborn dogs. Growth-retarded pups developed lower blood glucose levels after 3, 6, and 9 h of neonatal fasting, reduced plasma levels of free fatty acids (FFA) at 9 and 24 h, and lower ketone bodies at 24 h compared with age-matched newborn control pups. Systemic rates of palmitate and alanine turnover were not affected, but systemic glucose turnover was reduced for 3-9 h after birth. The rate of alanine incorporation into glucose from 3 to 9 h was also reduced in growth-retarded pups compared with timed controls. Paradoxically, the rate of incorporation of palmitate into triglycerides was augmented in the smaller growth-retarded pups. Hepatic glycogen content was reduced at every time in the study among growth-retarded pups, whereas the rates of glycogenolysis between birth and 24 h were equivalent in the two pup groups. In contrast, hepatic triglyceride levels were augmented throughout the study in pups with growth retardation. Maternal starvation and lower glucose levels resulted in a lower hepatic energy charge, and augmented cytoplasmic and mitochondrial NAD-to-NADH ratios in intrauterine growth-retarded pups. These data suggest that intrauterine growth retardation in dogs results in fasting neonatal hypoglycemia that is due in part to reduced systemic glucose production. We speculate that reduced rates of gluconeogenesis from alanine and reduced oxidation of alternate fuels such as FFA contribute to hypoglycemia. FFA recycling to triglyceride synthesis rather than oxidative pathways may contribute to the observed reduction of circulating glucose levels.
Kliegman
R M
RM
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
D000375:Aging; D000409:Alanine / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D004734:Energy Metabolism; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism; D007773:Lactates / Q000097:blood; D008099:Liver / Q000254:growth & development* / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D011247:Pregnancy; D012016:Reference Values; D014280:Triglycerides / Q000378:metabolism
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007657:Ketone Bodies; D007773:Lactates; D008112:Liver Glycogen; D014280:Triglycerides; D009243:NAD; D005947:Glucose; D000409:Alanine