Experimental Environment Is a Determinant of Gene Methylation and One-Carbon Metabolism in Obese Adult Mice
Bibliographic record
Abstract
BACKGROUND: Diet-induced obesity (DIO) leads to insulin resistance (IR) and alters gene expression through epigenetic mechanisms, including DNA methylation. Here, we aimed to investigate whether experimental environment is an important variable in determining DNA methylation and one-carbon metabolism in DIO mice fed a multi-vitamin-mineral mixture (MVM). METHODS: Three experiments with identical design were conducted in three independent animal facilities (i.e., experimental environments or locations). In each location, 12-week-old male C57BL/6J mice were randomly assigned to two dietary groups: high-fat (HF) and HF-MVM for an average of 10 weeks. Global and gene-specific methylation of adipose function related genes in epididymal white adipose tissue (eWAT), and insulin signaling genes in the liver were analyzed using bisulfite pyrosequencing. Hepatic 1-C metabolites were measured and the ratio of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) was used as an indicator of methylation potential. RESULTS: Experimental location affected global methylation patterns in the eWAT, but not in the liver. At the gene-specific level, experimental location, MVM, and their interaction altered the methylation of genes related to adipose function (Srebf1, Acaca, Fasn, Pparg, and Rbp4) in the eWAT and insulin signaling (Pi3kr1 and Akt1) in the liver (p < 0.05). The SAM/SAH ratio was correlated with gene-specific methylation at some CpG sites of Srebf1, Pi3kr1, Acaca, Fasn, Pparg, Rbp4, and Akt1) genes (p < 0.05). CONCLUSION: The experimental environment is a significant determinant of the effects of micronutrient supplement on 1-C metabolism and the methylation of genes associated with IR in tissues of DIO adult male mice.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".