Reduced Expression and Methylation of Soat2 in Liver From Mice with Hyperhomocysteinemia.
Bibliographic record
Abstract
Hyperhomocysteinemia (HHcy) is associated with alterations in liver lipid metabolism and this may contribute to the pathological effects of HHcy. The goal of this study was to determine if HHcy is associated with changes in liver cholesterol ester fatty acids and expression and methylation of the Soat2 gene. Soat2 encodes acyl‐coenzyme A:cholesterol acyltransferase 2 (ACAT2), which functions to catalyze the reaction responsible for the intracellular esterification of cholesterol with acyl‐CoA molecules, with oleoyl‐CoA the preferred substrate. Mice heterozygous for disruption of the gene for cystathionine‐(‐synthase (Cbs +/−) and C57BL/6 mice (Cbs +/+) were fed a control diet or a high methionine/low folate (HH) diet to induce HHcy. Levels of Soat2 mRNA (p<0.05) and ACAT protein (p<0.001) in liver were lower in Cbs +/− mice fed the HH diet with higher plasma total homocysteine levels than Cbs +/+ mice fed the control diet (35.01±5.6 vs 2.21±0.6 (M, respectively). Given we have previously shown that HHcy is accompanied by reduced tissue methylation capacity and changes in gene‐specific DNA methylation, we determined the methylation status of Soat2. In silico searches identified a CpG‐rich region in the 5′ upstream portion of the Soat2 gene and found that this region was 50% less methylated in Cbs +/− mice fed the HH diet than in Cbs +/+ mice fed the control diet. Total levels of cholesterol ester in liver were not different in mice with HHcy but levels of oleic acid were lower (p<0.05) in cholesterol esters from Cbs+/− mice fed the HH diet than Cbs+/+ mice fed the control diet. These findings are the first to show reduced methylation and expression of the Soat2 gene in a mouse model of HHcy and suggest role for changes in liver cholesterol ester 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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".