Liver‐specific phosphocholine cytidylyltransferase‐ α knockout mice develop insulin resistance despite having lower plasma lipid levels
Bibliographic record
Abstract
CTP: phosphocholine cytidylyltransferase (CT) is the key regulatory enzyme in the CDP‐choline pathway for the biosynthesis of phosphatidylcholine (PC). Hepatic cells can also synthesize PC via the sequential methylation of phophatidylethanolamine catalyzed by phosphatidylethanolamine N ‐methyltransferase (PEMT). To ascertain the functional importance of CTα, we previously created a mouse in which the hepatic CTα gene was specifically inactivated by the cre/loxP procedure. In the CTαknockout, hepatic CT activity was 20% of normal, while PEMT activity was elevated 2‐fold as compared to controls. Plasma PC concentration was reduced in the CTα knockout fed a chow diet, as were HDL (cholesterol and Apo A1) and VLDL (triacylglycerol and Apo B100) levels. Given the link between elevated plasma lipid levels and insulin resistance, we predicted that deleting hepatic CTα would prevent insulin resistance in mice fed a western diet (high fat/high carbohydrate). After 3 weeks, the CTαknockout mice, unexpectedly, gained more body weight than their control littermates, but continued to have lower plasma lipid levels (cholesterol, triacylglycerol, and non‐esterified fatty acids). Surprisingly, the knockout mice were more insulin resistant (as assessed by a glucose tolerance test) and had increased fasting blood glucose levels. The knockout mice also developed liver steatosis (10‐fold increase in triacylglycerol) and with concurrent liver damage (increased plasma alanine aminotransferase activity). Although the etiology of the insulin resistance is unknown, our results show that hepatic CTαis vital for normal lipid metabolism and insulin signaling.
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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) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".