Acute effects of fatty acids on autophagy in NPY neurones
Bibliographic record
Abstract
High-fat diet (HFD) feeding is deleterious to hypothalamic tissue, leading to inflammation and lipotoxicity, as well as contributing to central insulin resistance. Autophagy is a process that restores cellular homeostasis by degrading malfunctioning organelles and proteins. Chronic HFD-feeding down-regulates hypothalamic autophagy. However, the effects of short-term HFD-feeding and the saturated fatty acid palmitate (PA) on hypothalamic autophagy and in neurones that express neuropeptide Y (NPY) and agouti-related peptide remains unknown. Therefore, we assessed hypothalamic autophagy after 1 and 3 days of HFD-feeding. We also injected PA i.c.v and analysed the modulation of autophagy in hypothalamic tissue. Both interventions resulted in changes in autophagy-related gene profiles without significant differences in protein content of p62 and LC3B-II, markers of the autophagy pathway. When we assessed native NPY neurones in brain slices from PA-treated animals, we observed increased levels of Atg7 and LC3B protein in response to PA treatment, indicating the induction of autophagy. We then tested the direct effects of fatty acids using the immortalised hypothalamic NPY-expressing neuronal cell model mHypoE-46. We found that PA, but not palmitoleate (PO) (a monounsaturated fatty acid), was able to induce autophagy. Co-treatment with PA and PO was able to block the PA-mediated induction of autophagy, as assessed by flow cytometry. When the de novo ceramide synthesis pathway was blocked with myriocin pre-treatment, we observed a decrease in PA-mediated induction of autophagy, although there was no change with the toll-like receptor 4 inhibitor, TAK-242. Taken together, these findings provide evidence that saturated and unsaturated fatty acids can differentially regulate hypothalamic autophagy and that ceramide synthesis may be an important mediator of those effects. Understanding the mechanisms by which dietary fats affect autophagy in neurones involved in the control of energy homeostasis will provide potential new pathways for targeting and containing the obesity epidemic.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".