Changes in Liver Fads2 expression and Phospholipid Fatty Acids in Mice with Hyperhomocysteinemia
Bibliographic record
Abstract
Homocysteine is metabolically linked to methylation reactions through the methionine cycle and we have previously shown that hyperhomocysteinemia (HHcy) is accompanied by reduced tissue methylation capacity and altered DNA methylation. Phospholipids are substrates for methylation reactions with phosphatidylcholine (PC) produced following methylation of phosphatidylethanolamine (PE). PC and PE are integral membrane lipids in the liver and we hypothesize that some of the pathological effects of HHcy may be related to changes in PC and PE metabolism. The goal of the present study was to determine the effect of HHcy on liver phospholipids, phospholipid fatty acids and transcripts for Fads2, which functions to desaturate 18:2n‐6 and 18:3n‐3 to 20:4n‐6 and 22:6n‐3, respectively. Mice heterozygous for disruption of the gene for cystathionine‐β‐synthase ( Cbs +/−) and C57BL/6 mice ( Cbs +/+) were fed a control diet or a high methionine/low folate diet to induce HHcy (HH diet) for 8–12 months. We found a higher percentage of PE (32.0±0.6 vs 26.4±0.5, p<0.001) and lower percentage of PC (41.0±1.1 vs 45.6±0.3, p<0.01) in liver phospholipids of Cbs +/−mice fed the HH diet with HHcy (95±12μmol/L) than Cbs +/+ mice fed the control diet. This was accompanied by lower (p<0.01) 20:4n‐6 in PC and PE, higher (p<0.01) 22:6n‐3 in PE, and lower (p<0.05) levels of Fads2 transcripts in liver from Cbs +/− fed the HH diet than Cbs +/+ mice fed the control diet. These findings are the first to show altered liver phospholipid fatty acids and Fads2 transcripts in a mouse model of HHcy and suggest a role for changes in phospholipid fatty acid metabolism in the pathology of HHcy.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".