Abstract
Summary: The capacity for ketone synthesis by the liver is low for at least 8 h after delivery in newborn human infants. The present studies define developmental changes in hepatic ketogenesis in the newborn guinea pig with particular emphasis on whether there is a delay in development after birth and the site of developmental change. Studies in fresh liver homogenates indicated that the capacity to synthesize ketones from the oxidation of long-chain fatty acid (1 mM oleate plus 0.5 mM L-carnitine) was very low in term-fetal (5.4 ± 0.4) and newborn pups less than 12 h old (7.7 ± 1) compared to pups 24 or more h old (24–26) and adult guinea pigs (17.8 ± 0.3 μM/h/g). In contrast to the newborn rat, no developmental changes were observed in the carnitine content of tissues (liver, heart, skeletal muscle) or plasma in newborn guinea pigs. The developmental limitation in ketogenesis in the newborn guinea pig was not due to low activity of the enzymes of the hydroxymethylglutaryl-CoA pathway. More rapid rates of ketone production were found with 0.5 mM palmityl-carnitine in term-fetal (13.4 ± 1.7) and newborn pups less than 12 hours old (17.8–21 μM/h/g), suggesting that part of the limitation in ketone synthesis in the newborn guinea pig resides at the step of fattyacyl carnitine formation on the outer aspect of the inner mitochondrial membrane. The activity of this carnitine palmityl transferase (CPT1) was low in term fetal liver (1.0 ± 0.03 μM/h/g), remained low for 5–10 h after delivery, and then rose to 13 ± 0.7 μM/h/g at 24–48 h of age.
Evidence for at least two additional sites of developmental change in fatty acid oxidation was found in studies of ketogenesis from short-(butyrate)- and medium-(octanoate)-chain fatty acids. (1) In term-fetuses, ketone production from butyrate (17.8 ± 1.5 μM/h/g) was only half that found after 24–36 h of age (36 ± 3.8 μM/h/g), suggesting a limitation in the intramitochondrial beta-oxidation capacity. (2) In adult guinea pigs and in pups 8–10 days old, ketone synthesis from octanoate was 40–45 μM/h/g compared to 4.1 ± .8 μM/h/g in term-fetuses. At 24–36 h old, carnitine-stimulated ketone production from octanoate from 2.4 ± 2.1 to 37 ± 0.9 μM/h/g. This third site of developmental change in hepatic ketogenesis may involve the intramitochondrial activating step for medium-chain fatty acids.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stanley, C., Gonzales, E. & Baker, L. Development of Hepatic Fatty Acid Oxidation and Ketogenesis in the Newborn Guinea Pig. Pediatr Res 17, 224–229 (1983). https://doi.org/10.1203/00006450-198303000-00012
Issue Date:
DOI: https://doi.org/10.1203/00006450-198303000-00012
This article is cited by
-
Phospholipid composition of neonatal guinea pig liver and plasma: Effect of postnatal food restriction
Lipids (1996)
-
Neonatal enterovirus infection
The Indian Journal of Pediatrics (1988)