Ketogenesis from Lactate in Rat Liver during the Perinatal Period

Abstract

ABSTRACT. Lactate, which accumulates in neonatal plasma during the first hours after delivery, is used by neonatal tissues as a source of energy and carbon skeleton. In this work, lactate use by rat liver during late gestation (last 3 d) and early neonatal life (6 h postpartum) has been studied. The rate of lactate use by liver was compared with that found with oleate, inasmuch as fatty acids are the main substrates for the liver after the onset of lactation. The main fate of lactate in the liver during the perinatal period was ketone bodies, preferentially over C 0 2 and lipids. The rate of oxidation of lactate and its incorporation into lipids decreased during late gestation, but the rate of ketogenesis from lactate remained high during this period. After birth, the rate of lactate oxidation sharply increased, but lipogenesis decreased and ketogenesis was maintained. The rates of oleate oxidation and ketogenesis from oleate were two orders of magnitude lower than those from lactate. However, the rate of oleate incorporation into lipids was only 4-fold lower than that observed from lactate under the same circumstances. Our results suggest that lactate is a major substrate for the liver during the perinatal period because it is mainly incorporated into ketone bodies. This may target lactate carbons to different neonatal tissues. During the late stages of gestation, the rat fetus accumulates a substantial amount of lactate (I), probably as a consequence of the activity of anaerobic glycolysis in the placenta (2, 3) and, possibly, in some maternal (4) and fetal tissues (5). During the immediate postnatal period, blood lactate concentrations increase further, but lactate is rapidly removed during the first 2 h of extrauterine life in the rat (1, 6) and human baby (7). Lactate is therefore available as a putative metabolic fuel throughout the perinatal period. It has been reported that lactate is used during the perinatal period by rat lung (8) and brain (2, 9, 10) and by dog (1 1) and human (12) brain. This suggests that lactate may play an important role in fuel supply to fetal and neonatal tissues during the perinatal period (1 3).Because the overall rate of lactate use after delivery is very high (14) and cannot only be accounted for by the rates of use in brain (10) and lung (S), we were prompted to investigate the possible role of the liver in lactate metabolism during the perinatal period. We have previously reported (15) that early neonatal liver uses lactate as a source of energy and carbon skeleton preferentially over glucose or oleate. The present work investigated the time-course of lactate use by the liver during the perinatal period. MATERIALS AND METHODSReagents. Enzymes were obtained from Boehringer (Mannheim, Germany). Coenzymes, oleic acid, and essentially fatty acid-free albumin were purchased from Sigma Chemical Co. (St. Louis, MO). L-Lactic acid was obtained from Serva Feinbiochemica (Heidelberg, Germany). Radioactive substrates were obtained from New England Nuclear (Boston, MA).Animals. Albino...

Metabolic fuel utilization and pyruvate oxidation during the postnatal period

“…Accordingly, it has been reported that neonatal lung (Patterson et al 1986), heart (E. Fern~dez and J.M. Medina, unpublished results) and liver (Almeida et al 1992) utilize lactate for energy production and/or lipogenic purposes. However, special attention has also been paid to lactate utilization by the brain, probably because this organ has to continue its development even under the starvation occurring during the presuckling period.…”