Adaptation to Choline Deprivation: Choline Redistribution and Choline Storage
Bibliographic record
Abstract
In mammals, the only endogenous pathway for choline biosynthesis is the methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) by PE N ‐methyltransferase (PEMT). Complete choline deprivation achieved by feeding Pemt −/− mice a choline‐deficient (CD) diet is lethal due to liver failure. However, CD mice that lack both PEMT and multiple drug resistant protein 2 (MDR2) are resistant to liver failure and survive for at least 3 months. This allowed us to uncover several new adaptations to choline deprivation besides classical adaptations such as up‐regulation of PEMT. The newly found adaptations to choline deprivation include choline recycling, maintenance of membrane integrity via maintenance of PC/PE ratio, and choline redistribution and choline storage that is the main focus of this presentation. Total choline‐containing metabolites in the liver of CD‐ Mdr2 −/− /Pemt −/− mice were maintained via down‐regulation of choline oxidation suggesting that liver could obtain choline from extrahepatic sources. By in vivo injection of [ 3 H]choline into CD‐ Mdr2 −/− /Pemt −/− mice, we found the existence of choline redistribution from muscle to liver and brain. Although CD‐ Pemt −/− mice failed to adapt to choline deprivation, it was intriguing to explore whether or not these mice had adaptive response to choline deprivation. Interestingly, we found that female Pemt −/− mice showed one‐day delay of liver damage as compared to male Pemt −/− mice when fed the CD diet. This allowed us to show that in response to choline deprivation, mice can mobilize extrahepatic PC to liver via enhancing HDL‐PC efflux and the tissues for enhanced HDL‐PC efflux are sites of choline storage. However, choline is stored and can be supplied, unlike fat and glycogen, in mice for only one day during choline deprivation. (Funded by CIHR)
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".