Integrated Substrate Utilization by Perinatal Lung

Patterson, Carolyn E.; Koniki, Mark V.; Selig, William M.; Owens, Connie M.; Rhoades, Rodney A.

doi:10.3109/01902148609057504

Cited by 15 publications

(5 citation statements)

References 29 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: 57%

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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: 57%

“…13) and lung (8). The results of the study presented here show that lactate is also an important substrate for neonatal liver; it is used as an energy source and also as a precursor of lipids and ketone bodies.…”

Section: Discussionmentioning

confidence: 79%

Ketogenesis from Lactate in Rat Liver during the Perinatal Period

1992

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“…Based on perfused lung studies, ATII cells may also utilize lactate delivered in pulmonary circulation. Multiple investigators have demonstrated lactic acid uptake from pulmonary circulation (20), oxidization (7,31,34), and incorporation into lung lipids (28,31). In this manner, local metabolic cooperation between lung cell phenotypes may form a key component of normal alveolar tissue homeostasis, providing substrate for ATII cell energy and lipid production while also preventing lactic acid build-up.…”

Section: Discussionmentioning

confidence: 99%

Lactate as substrate for mitochondrial respiration in alveolar epithelial type II cells

Lottes

Newton

Spyropoulos

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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Lottes RG, Newton DA, Spyropoulos DD, Baatz JE. Lactate as substrate for mitochondrial respiration in alveolar epithelial type II cells. Am J Physiol Lung Cell Mol Physiol 308: L953-L961, 2015. First published March 6, 2015 doi:10.1152/ajplung.00335.2014.-Because of the many energy-demanding functions they perform and their physical location in the lung, alveolar epithelial type II (ATII) cells have a rapid cellular metabolism and the potential to influence substrate availability and bioenergetics both locally in the lung and throughout the body. A thorough understanding of ATII cell metabolic function in the healthy lung is necessary for determining how metabolic changes may contribute to pulmonary disease pathogenesis; however, lung metabolism is poorly understood at the cellular level. Here, we examine lactate utilization by primary ATII cells and the ATII model cell line, MLE-15, and link lactate consumption directly to mitochondrial ATP generation. ATII cells cultured in lactate undergo mitochondrial respiration at near-maximal levels, two times the rates of those grown in glucose, and oxygen consumption under these conditions is directly linked to mitochondrial ATP generation. When both lactate and glucose are available as metabolic substrate, the presence of lactate alters glucose metabolism in ATII to favor reduced glycolytic function in a dose-dependent manner, suggesting that lactate is used in addition to glucose when both substrates are available. Lactate use by ATII mitochondria is dependent on monocarboxylate transporter (MCT)-mediated import, and ATII cells express MCT1, the isoform that mediates lactate import by cells in other lactate-consuming tissues. The balance of lactate production and consumption may play an important role in the maintenance of healthy lung homeostasis, whereas disruption of lactate consumption by factors that impair mitochondrial metabolism, such as hypoxia, may contribute to lactic acid build-up in disease. mitochondrial function; metabolism; hypoxia FROM A METABOLIC perspective, the lung is a unique physiological environment. The cells that compose the alveolar epithelium form the barrier between external air and the pulmonary vasculature in the best-oxygenated environment in the body. While terminally differentiated alveolar epithelial type I (ATI) cells form the passive surface across which gas exchange occurs, alveolar epithelial type II (ATII) cells perform a variety of energetically costly functions, including pulmonary surfactant production (16), fluid transport and homeostasis (27), immune functions (6, 23), and progenitor roles for self-renewal and transdifferentiation to repopulate ATI cells (5, 19). Additionally, the lung is the only organ apart from the heart itself that receives the entire cardiac output upon every passage through the body. Metabolic activity in the cells that compose the alveolar epithelium could potentially influence substrate availability, energy production, and redox balance locally and throughout the whole body (20, 32). While the lung...

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“…Alternative routes for glucose metabolism, which may also become more active, include the citric acid cycle and the pentosephosphate shunt pathway (1 8). Increased citric acid cycle activity has been found in fetal rat lung slices taken from animals near term (18). This activity would logically increase in vivo near term, coincident with the increase in pulmonary oxygen delivery and use that we have described (1).…”

Section: Discussionmentioning

confidence: 99%

Late Gestation Alterations in Fetal Pulmonary Lactate Metabolism in Vivo

Simmons

Charlton

1990

Pediatr Res

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ABSTRACT. We have previously shown that lactate is produced by the ovine fetal lung. Inasmuch as factors that might affect lactate production, such as pulmonary glucose and oxygen uptake, change late in gestation we investigated whether pulmonary lactate metabolism also changes. Eleven chronically catheterized fetal lambs were studied over 119-141 d gestation. Lactate, glucose, and oxygen concentrations were measured in the pulmonary artery (PA) and vein while lung blood flow was determined using labeled microspheres. Between early studies (5127 d) and studies near term (2134 d) PA lactate levels did not change, but due to increasing pulmonary blood flow, lung lactate delivery rose 51% ( p < 0.05). Because of a decline in PA glucose, lactate also made up a larger fraction of the major nonnitrogenous substrate in PA blood near term ( p < 0.001). Despite this, no net pulmonary uptake of lactate occurred. Lactate production continued, but decreased by 80% between early and late studies ( p < 0.05) and the maximum fraction of glucose uptake that could be accounted for by lactate production dropped from 0.78 to 0.20 ( p < 0.025). Correlations were found between lung lactate production and both glucose delivery ( p < 0.005) and PA glucose concentration ( p < 0.05). The ratio between lactate production and glucose uptake also correlated with PA glucose ( p < 0.05). No relationships were observed between lactate production and PA oxygen content, oxygen delivery, lactate concentration, or lactate delivery. The decreasing fraction of glucose uptake explained by lactate production suggests that metabolism of pulmonary glucose is altered near term. The correlation between decreasing glucose delivery and declining lactate production also suggests that glucose itself influences this change. (Pediatr Res 27: 274-277,1990) Abbreviations PA, pulmonary artery PV, pulmonary vein In previous studies in chronically catheterized fetal sheep, we found that glucose is taken up by the fetal lung and lactate is produced (1). During late gestation, the average quantity of lactate produced is equivalent to about 50% of pulmonary glucose uptake. However, metabolic factors that may influence lung lactate metabolism are not static during gestation. Near term, Received March 20, 1989; accepted October 19, 1989 pulmonary arterial glucose concentration and pulmonary glucose uptake decline, whereas pulmonary delivery of oxygen increases (1). We, therefore, investigated whether lactate metabolism in the fetal lung changes with gestation or with either pulmonary delivery of glucose or oxygen. Further, because lactate levels themselves might affect lung metabolism, we investigated the relationship between pulmonary lactate concentration and both lung lactate production and glucose use. MATERIALS AND METHODS Surgical preparation and recovery. Eleven mixed Western,breed-dated, pregnant sheep of 115 to 125 d gestation were surgically prepared by methods described previously (1-3). With the ewe under spinal anesthesia (induced by 1 % tetracaine) and ...

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Integrated Substrate Utilization by Perinatal Lung

Cited by 15 publications

References 29 publications

Ketogenesis from Lactate in Rat Liver during the Perinatal Period

Ketogenesis from Lactate in Rat Liver during the Perinatal Period

Lactate as substrate for mitochondrial respiration in alveolar epithelial type II cells

Late Gestation Alterations in Fetal Pulmonary Lactate Metabolism in Vivo

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