Choline Kinetics in Neonatal Liver, Brain and Lung—Lessons from a Rodent Model for Neonatal Care
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 invest...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/3/720 |
| _version_ | 1797485491535216640 |
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| author | Wolfgang Bernhard Marco Raith Anna Shunova Stephan Lorenz Katrin Böckmann Michaela Minarski Christian F. Poets Axel R. Franz |
| author_facet | Wolfgang Bernhard Marco Raith Anna Shunova Stephan Lorenz Katrin Böckmann Michaela Minarski Christian F. Poets Axel R. Franz |
| author_sort | Wolfgang Bernhard |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T23:20:31Z |
| format | Article |
| id | doaj.art-6dc1999face14aa2a9efe671f00697f8 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T23:20:31Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-6dc1999face14aa2a9efe671f00697f82023-11-23T17:28:30ZengMDPI AGNutrients2072-66432022-02-0114372010.3390/nu14030720Choline Kinetics in Neonatal Liver, Brain and Lung—Lessons from a Rodent Model for Neonatal CareWolfgang Bernhard0Marco Raith1Anna Shunova2Stephan Lorenz3Katrin Böckmann4Michaela Minarski5Christian F. Poets6Axel R. Franz7Department of Neonatology, University Children’s Hospital, Tübingen University Hospital, 72076 Tübingen, Baden-Wuerttemberg, GermanyMax-Planck-Institut für Psychiatrie, 80804 Munich, Bavaria, GermanyDepartment of Neonatology, University Children’s Hospital, Tübingen University Hospital, 72076 Tübingen, Baden-Wuerttemberg, GermanyDepartment of Neonatology, University Children’s Hospital, Tübingen University Hospital, 72076 Tübingen, Baden-Wuerttemberg, GermanyDepartment of Neonatology, University Children’s Hospital, Tübingen University Hospital, 72076 Tübingen, Baden-Wuerttemberg, GermanyDepartment of Neonatology, University Children’s Hospital, Tübingen University Hospital, 72076 Tübingen, Baden-Wuerttemberg, GermanyDepartment of Neonatology, University Children’s Hospital, Tübingen University Hospital, 72076 Tübingen, Baden-Wuerttemberg, GermanyDepartment of Neonatology, University Children’s Hospital, Tübingen University Hospital, 72076 Tübingen, Baden-Wuerttemberg, GermanyCholine 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.https://www.mdpi.com/2072-6643/14/3/720betainebraincholinephospholipidsliverlung |
| spellingShingle | Wolfgang Bernhard Marco Raith Anna Shunova Stephan Lorenz Katrin Böckmann Michaela Minarski Christian F. Poets Axel R. Franz Choline Kinetics in Neonatal Liver, Brain and Lung—Lessons from a Rodent Model for Neonatal Care Nutrients betaine brain choline phospholipids liver lung |
| title | Choline Kinetics in Neonatal Liver, Brain and Lung—Lessons from a Rodent Model for Neonatal Care |
| title_full | Choline Kinetics in Neonatal Liver, Brain and Lung—Lessons from a Rodent Model for Neonatal Care |
| title_fullStr | Choline Kinetics in Neonatal Liver, Brain and Lung—Lessons from a Rodent Model for Neonatal Care |
| title_full_unstemmed | Choline Kinetics in Neonatal Liver, Brain and Lung—Lessons from a Rodent Model for Neonatal Care |
| title_short | Choline Kinetics in Neonatal Liver, Brain and Lung—Lessons from a Rodent Model for Neonatal Care |
| title_sort | choline kinetics in neonatal liver brain and lung lessons from a rodent model for neonatal care |
| topic | betaine brain choline phospholipids liver lung |
| url | https://www.mdpi.com/2072-6643/14/3/720 |
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