Acetoacetate metabolism in infant and adult rat brain <i>in vitro</i>

Itoh, Tadao; Quastel, J. H.

doi:10.1042/bj1160641

Cited by 158 publications

(62 citation statements)

References 33 publications

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“…There is considerable evidence to suggest that lactate plays a relevant role in the homeostasis mechanisms of fuel supply to tissues during the perinatal period. Thus, it has been reported that lactate is used by rat lung (8), heart (Fernandez E, Medina JM, personal communication), and brain (2,9,10,33). The present results suggest that rat liver also uses lactate during the perinatal period.…”

Section: Rate Of Lipogenesissupporting

confidence: 56%

Ketogenesis from Lactate in Rat Liver during the Perinatal Period

1992

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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...

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Section: Rate Of Lipogenesissupporting

confidence: 56%

Ketogenesis from Lactate in Rat Liver during the Perinatal Period

1992

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“…In the present study, the rate of lactate utilization remained high during the last day of gestation, whereas the rates of glucose or 3-hydroxybutyrate utilization decreased (Table l), suggesting that lactate may be the main substrate utilized by the brain around birth. It should be noted that lactate may also support part of the energy requirements during the suckling period, as has been reported for rat (14,24), mouse (25), and dog brain (26), because this substrate was preferred to glucose during hypoxia and recovery (2 1) and during hypoglycemia (25,26).…”

Section: Separation Of Phospholipids By Hplc Phospholipid Speciesmentioning

confidence: 97%

“…Preliminary experiments have shown that, under our experimental conditions, the I4CO2 evoked was proportional to the weight of tissue in the range of 40-100 mg/flask and was linear over 2 h (1 1). The width of the slice (approximately 0.5 mm) has been shown to be sufficiently thin to allow an adequate oxygenation of the brain cells (14).…”

Section: Reagents L-[u-'4c]lactate (177 CImentioning

confidence: 99%

Lipogenesis from Lactate in Fetal Rat Brain during Late Gestation

Bolaños

Medina

1993

Pediatr Res

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ABSTRACT. Much evidence suggests that lactate may play a relevant role as a metabolic substrate for the brain immediately after delivery. In this work, the rate of lactate, glucose, and 3-hydroxybutyrate incorporation into COz, phospholipids, and sterols was studied in fetal rat brain slices during the last 3 d of gestation. Lactate was the best substrate for the brain during the late gestation, not only as a source of energy, but also as precursor of brain phospholipids and sterols. The rates of oxidation and lipogenesis from glucose and 3-hydroxybutyrate showed a progressive decrease during late gestation (10-15% reduction on d 2 0 . 5 ,~ < 0.05, and 22-33% on d 21.5, p < 0.01, for oxidation; 14-18% on d 20.5, p < 0.05, and 20-22% on d 21.5, p < 0.05, for lipogenesis), whereas lactate maintained its rate of utilization in the same circumstances. The main phospholipid synthesized throughout the late gestation was phosphatidylcholine. The synthesis of phosphatidylcholine and phosphatidylethanolamine from lactate, glucose, and 3-hydrokybutyrate decreased during late gestation. Under these circumstances. however. the rate of ~h~s~hatidylserine synthesis from gl"cose was'un~han~ed; it decreased from 3-hydroxybutyrate and increased from lactate. The rate of desmosterol synthesis was about 3-to 4-fold higher than those of cholesterol and lanosterol. Our results suggest that the capacity of fetal brain for lactate utilization remains high during late gestation, but the capacities for the utilization of glucose and 3-hydroxybutyrate decrease until term. This may indicate that lactate is an important substrate for brain development during late gestation. (Pediatr Res 33: 66-71, 1993) Abbreviations PC, pbosphatidylcholine PE, phosphatidylethanolamine PI, phosphatidylinositol PS, phosphatidylserine It is well established that ketone bodies (3-hydroxybutyrate and acetoacetate) are important substrates for the developing brain and that, together with glucose, they are able to meet most of the brain's metabolic requirements during the suckling period (1). However, just before the onset of lactation, i.e. during the presuckling period, there is a very low concentration of ketone bodies in rat blood (2). Moreover, the newborn rat shows a

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“…Consequently, the possibility was tested that compartmentation also occurs in the oxidative metabolism of glutamate and glutamine. Ketone bodies serve as a primary metabolic energy source in the developing brain (Itoh and Quastel, 1970;Hawkins et al, 1971). In the mature brain, glucose is the primary energy source (Sokoloff, 1960).…”

Section: Discussionmentioning

confidence: 99%

Compartmentation of [¹⁴C]Glutamate and [¹⁴C]Glutamine Oxidative Metabolism in the Rat Hippocampus as Determined by Microdialysis

Zielke

Collins

Baab

et al. 1998

Journal of Neurochemistry

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Metabolic compartmentation of amino acid metabolism in brain is exemplified by the differential synthesis of glutamate and glutamine from the identical precursor and by the localization of the enzyme glutamine synthetase in glial cells. In the current study, we determined if the oxidative metabolism of glutamate and glutamine was also compartmentalized. The relative oxidation rates of glutamate and glutamine in the hippocampus of free-moving rats was determined by using microdialysis both to infuse the radioactive substrate and to collect 14C0 2 generated during their oxidation. At the end of the oxidation experiment, the radioactive substrate was replaced by artificial CSF, 2 mm-fractions were collected, and the specific activities of glutamate and glutamine were determined. Extrapolation of the specific activity back to the time that artificial CSF replaced 14C-amino acids in the microdialysis probe yielded an approximation of the interstitial specific activity during the oxidation. The extrapolated interstitial specific activities for [14C]glutamate and [14C]glutamine were 59 ± 18 and 2.1 ±0.5 dpm/pmol, respectively. The initial infused specific activities for [U-140] glutamate and [U-14C] glutamine were 408 ±8 and 387 ±1 dpm/pmol, respectively. The dilution of glutamine was greater than that of glutamate, consistent with the difference in concentrations of these amino acids in the interstitial space. Based on the extrapolated interstitial specific activities, the rate of glutamine oxidation exceeds that of glutamate oxidation by a factor of 5.3. These data indicate compartmentation of either uptake and/or oxidative metabolism of these two amino acids. The presence of [14C}glutamine in the interstitial space when [14C]glutamate was perfused into the brain provided further evidence for the glutamate/glutamine cycle in brain. Key Words: Brain energy metabolism-Oxidation -Microdialysis-Glutamate-Glutamine.

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Acetoacetate metabolism in infant and adult rat brain in vitro

Cited by 158 publications

References 33 publications

Ketogenesis from Lactate in Rat Liver during the Perinatal Period

Ketogenesis from Lactate in Rat Liver during the Perinatal Period

Lipogenesis from Lactate in Fetal Rat Brain during Late Gestation

Compartmentation of [¹⁴C]Glutamate and [¹⁴C]Glutamine Oxidative Metabolism in the Rat Hippocampus as Determined by Microdialysis

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Acetoacetate metabolism in infant and adult rat brain in vitro

Cited by 158 publications

References 33 publications

Ketogenesis from Lactate in Rat Liver during the Perinatal Period

Ketogenesis from Lactate in Rat Liver during the Perinatal Period

Lipogenesis from Lactate in Fetal Rat Brain during Late Gestation

Compartmentation of [14C]Glutamate and [14C]Glutamine Oxidative Metabolism in the Rat Hippocampus as Determined by Microdialysis

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Compartmentation of [¹⁴C]Glutamate and [¹⁴C]Glutamine Oxidative Metabolism in the Rat Hippocampus as Determined by Microdialysis