Tamoxifen Induces Triacylglycerol Accumulation in the Mouse Liver by Activation of Fatty Acid Synthesis
Bibliographic record
Abstract
UNLABELLED: Tamoxifen is an anti-estrogen drug widely used for the treatment of hormone-sensitive breast cancer. Approximately 43% of breast cancer patients treated with tamoxifen develop hepatic steatosis. The mechanism or mechanisms by which tamoxifen may induce lipid accumulation in the liver are unclear. Mice were injected with tamoxifen or vehicle (sesame oil containing 1% benzyl alcohol) for 5 consecutive days. In comparison with the vehicle, tamoxifen increased hepatic triacylglycerol levels by 72%. The levels of plasma triacylglycerol were similar between the tamoxifen-treated and control groups. We found increased radiolabeling of triacylglycerol and phospholipids from [(3)H]acetate (∼50%) but not [(14)C]oleate in hepatocytes from tamoxifen-treated mice versus control mice. Fatty acid uptake, triacylglycerol secretion, and fatty acid oxidation remained unchanged in isolated hepatocytes after tamoxifen treatment. The apparent increase in fatty acid synthesis was explained by a marked decrease in the phosphorylation of acetyl coenzyme A carboxylase, which resulted in its activation. CONCLUSION: Our data suggest that increased de novo fatty acid synthesis is the primary event leading to tamoxifen-induced steatosis in the mouse liver. Inhibition of fatty acid synthesis might, therefore, ameliorate steatosis/steatohepatitis in breast cancer patients treated with tamoxifen.
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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".