Substrate Utilization for Phosphatidylcholine Synthesis by Type II Pneumocytes of Neonatal Rats

Abstract

ABSTRACT. Type I1 pneumocytes isolated from neonatal rat lungs, using an isolation procedure developed for adult rats, were found to be phenotypically stable and metabolically active in culture. The cells, purified by metrizamide gradient centrifugation and differential adherence, were capable of synthesizing phospholipids from 14C-labeled choline, palmitate, glucose, and acetoacetate. Regardless of the 14C-labeled substrates used, greater than two thirds of the radioactivity incorporated into phosphatidylcholine was recovered in disaturated phosphatidylcholine, the major component of surfactant phospholipids. The incorporation of palmitate into phosphatidylcholine and other phospholipids (i.e. phosphatidyl-ethanolamine, -glycerol, -serine, and -inositol) indicates that the neonatal type I1 cells have the capacity to produce surfactant lipids. The neonatal cells preferentially utilized acetoacetate over glucose as a precursor of phospholipids. In the adult type I1 cells, glucose was incorporated into phospholipids more rapidly than acetoacetate. The rate of glucose incorporation in the neonatal cells was enhanced by exogenous insulin. The preferential utilization of acetoacetate by the neonatal type I1 cells is consistent with the stimulated acetoacetyl CoA synthetase pathway in the lung. The depressed glucose incorporation into phospholipid, on the other hand, may be attributed to insulin insufficiency in the neonate. (Pediatr Res 30: [55][56][57][58][59][60][61]1991) Abbreviations PS, phosphatidylserine PE, phosphatidylethanolamine PG, phosphatidylglycerol PA, phosphatidic acid PC, phosphatidylcholine DSPC, disaturated PC USPC, unsaturated PC HBSS, Hanks' balanced salt solution Pulmonary surfactant, a lipoprotein complex, is essential for maintaining lung function by stabilizing the alveoli and preventing alveolar collapse (1). Insufficiency of surfactant is a leading cause of respiratory distress syndrome in newborns, particularly in premature infants (2). The amount of surfactant available to the alveoli depends upon its synthesis and secretion by type I1 pneumocytes (3, 4). Since the development of cell isolation techniques (5), type I1 cells have been widely used for studying the regulation of surfactant metabolism in adult and fetal animals (6, 7); however, little attention has been focused on newborns.Metabolic adaptation occurs during the postnatal period when neonates are shifted from a prenatal high-carbohydrate diet to a high-fat diet (8). Accordingly, there are increases in blood concentrations of fatty acids and ketone bodies and a reduction in glucose (9, 10). These changes are accompanied by enhanced utilization of fatty acids and ketone bodies for energy and lipid synthesis by neonatal brain and lung (1 1, 12). It may be reasoned that surfactant phospholipid production is also adapted to the changes in substrate availability in newborns. The present study was undertaken to establish whether neonatal type I1 pneumocytes, isolated according to the method developed for adult cell isolation (1 3)...

Hyperoxia-induced methylation decreases RUNX3 in a newborn rat model of bronchopulmonary dysplasia

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The lipogenic enzyme acetoacetyl-CoA synthetase and ketone body utilization for denovo lipid synthesis, a review

“…Regardless of age, AcAc was a better substrate for lipid synthesis than glucose ( 50 , 62 , 63 , 64 , 67 , 68 )…”

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