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Choline redistribution during adaptation to choline deprivation
Zhaoyu Li1, Luis B Agellon, Dennis E Vance
1Department of Biochemistry and Canadian Institutes of Health Research Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
The Journal of Biological Chemistry
|February 7, 2007
Summary
Mice lacking PEMT and MDR2 adapt to choline deprivation through tissue redistribution, not just liver recycling. This finding reveals a whole-body mechanism for maintaining essential choline levels.
Area of Science:
- Biochemistry
- Nutritional Science
- Physiology
Background:
- Choline is a vital nutrient for mammals, essential for various metabolic processes.
- Phosphatidylcholine synthesized in the liver is a primary source of endogenous choline via phosphatidylethanolamine N-methyltransferase (PEMT).
- Complete choline deprivation is lethal in mice due to liver failure, highlighting the critical role of choline homeostasis.
Purpose of the Study:
- To investigate novel mechanisms of adaptation to choline deprivation beyond hepatic choline recycling.
- To explore the role of choline redistribution in maintaining choline homeostasis in the whole animal.
- To identify previously undetected choline metabolic pathways in the brain.
Main Methods:
- Utilizing genetically modified mice (Mdr2(-/-)/Pemt(-/-)) to study adaptation to choline deficiency.
- Administering a choline-deficient diet and tracking choline metabolite levels in plasma and brain.
- Employing radiolabeled choline ([3H]choline) to trace choline distribution among different tissues.
Main Results:
- Mice lacking both PEMT and MDR2 maintained normal brain choline metabolites for 90 days on a choline-deficient diet.
- Plasma choline levels remained stable, while plasma phosphatidylcholine decreased significantly (>60%) in these mice.
- Choline redistribution among tissues was observed, and previously undetected choline oxidase activity was noted in the brain.
Conclusions:
- Adaptation to choline deprivation involves whole-body choline redistribution, complementing hepatic choline recycling.
- This study reveals a novel mechanism for maintaining brain choline levels under severe dietary restriction.
- Choline redistribution is a critical survival strategy, extending beyond the liver to the entire organism.
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