Abstract
Choline requirements are high in the rapidly growing fetus and preterm infant, mainly serving phosphatidylcholine (PC) synthesis for parenchymal growth and one-carbon metabolism via betaine. However, choline metabolism in critical organs during rapid growth is poorly understood. Therefore, we investigated the kinetics of D9-choline and its metabolites in the liver, plasma, brain and lung in 14 d old rats. Animals were intraperitoneally injected with 50 mg/kg D9-choline chloride and sacrificed after 1.5 h, 6 h and 24 h. Liver, plasma, lungs, cerebrum and cerebellum were analyzed for D9-choline metabolites, using tandem mass spectrometry. In target organs, D9-PC and D9-betaine comprised 15.1 ± 1.3% and 9.9 ± 1.2% of applied D9-choline at 1.5 h. D9-PC peaked at 1.5 h in all organs, and decreased from 1.5–6 h in the liver and lung, but not in the brain. Whereas D9-labeled PC precursors were virtually absent beyond 6 h, D9-PC increased in the brain and lung from 6 h to 24 h (9- and 2.5-fold, respectively) at the expense of the liver, suggesting PC uptake from the liver via plasma rather than local synthesis. Kinetics of D9-PC sub-groups suggested preferential hepatic secretion of linoleoyl-PC and acyl remodeling in target organs. D9-betaine showed rapid turnover and served low-level endogenous (D3-)choline synthesis. In conclusion, in neonatal rats, exogenous choline is rapidly metabolized to PC by all organs. The liver supplies the brain and lung directly with PC, followed by organotypic acyl remodeling. A major fraction of choline is converted to betaine, feeding the one-carbon pool and this must be taken into account when calculating choline requirements.
Highlights
Total weights of investigated organs and plasma comprised 15.6 ± 0.2% of this value, whereas their total cholinecontaining phospholipids amounted to 61.3 ± 3.9 μmol (Table 1), which is 21.7 ± 1.4% of the mean estimated choline-containing phospholipid pool (10 μmol/g) [1]
The total choline pool was low in plasma compared to other organs, its plasma concentration was 35 ± 3μM, i.e., in the same range as in the human fetus [2]
We found no sex differences of plasma choline in human cord blood before 37 wk postmenstrual age (PMA), and later on, lower values of female fetuses fairly exceeded those of preterm infants and their mothers, suggesting that sex differences are of minor relevance here [2]
Summary
Impact of Choline Metabolism on Preterm Infant Development. Choline is an essential nutrient and constitutive tissue component, with high and tightly regulated concentrations, in the parenchyma. Requirements are high in the fetus and preterm infant due to their 3–4-fold higher physiologic growth rate compared to the term born. Placental choline transfer is high, and plasma choline is
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