Inhibition of Insulin and T<sub>3</sub>‐Induced Fatty Acid Synthase by Hexanoate
Bibliographic record
Abstract
Fatty acid synthase (FAS) is responsible for the de novo synthesis of palmitate and stearate. This enzyme is activated by insulin and T(3), and inhibited by fatty acids. In this study, we show that insulin and T(3) have an inducing effect on FAS enzymatic activity, which is synergetic when both hormones are present. Octanoate and hexanoate specifically inhibit this hormonal effect. A similar inhibitory effect is observed at the level of protein expression. Transient transfections in HepG2 cells revealed that hexanoate inhibits, at least in part, FAS at a transcriptional level targeting the T(3) response element (TRE) on the FAS promoter. The effect of C6 on FAS expression cannot be attributed to a modification of insulin receptor activation or to a decrease in T(3) entry in the cells. Using bromo-hexanoate, we determined that hexanoate needs to undergo a transformation in order to have an effect. When incubating cells with triglyceride-hexanoate or carnitine-hexanoate, no effect on the enzymatic activity induced by insulin and T(3) is observed. A similar result was obtained when cells were incubated with betulinic acid, an inhibitor of the diacylglycerol acyltransferase. However, the incubation of cells with Triacsin C, a general inhibitor of acyl-CoA synthetases, completely reversed the inhibitory effect of hexanoate. Our results suggest that in hepatic cells, hexanoate needs to be activated into a CoA derivative in order to inhibit the insulin and T(3)-induced FAS expression. This effect is partially transcriptional, targeting the TRE on the FAS promoter.
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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".