Farnesol inhibits fatty acid synthase expression and activity via a 9‐cis retinoic acid‐dependent mechanism
Bibliographic record
Abstract
Farnesol is a metabolite of the mevalonate/cholesterol biosynthetic pathway that is produced endogenously in cells and is also present in dietary fruits and vegetables. Recently, farnesol has been shown to inhibit de novo triglyceride synthesis in hepatocytes although the molecular mechanism mediating this effect has not been reported. We treated MCF‐7 human breast cancer cells and rat hepatocytes with farnesol and found decreased fatty acid synthase (FAS) activity that was mediated by lower mRNA and protein levels. Farnesol has previously been shown to regulate activity of the farnesoid X receptor, peroxisome proliferator‐activated receptor alpha and thyroid hormone receptor beta 1. We investigated whether regulation of these nuclear hormone receptors may mediate effects of farnesol on FAS mRNA expression in rat hepatocytes but found no evidence of regulation through these transcription factors. We did, however, observe a complete restoration of FAS mRNA levels in cells treated concomitantly with farnesol and 9‐cis retinoic acid (RA), while treatment of control cells with 9‐cis RA alone had no effect. Although decreased retinoid X receptor (RXR) beta protein levels were apparent by 48 h in cells treated with farnesol, this could not explain effects of farnesol on FAS that were observed already by 24 h. We conclude that farnesol inhibits FAS at the level of transcription and that this effect appears to be mediated by decreased RXR activation.
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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 | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".