Abstract 13917: <i>O</i> -GlcNAc Levels Are Regulated in a Time and Tissue Specific Manner Independently of Dietary Intake
Bibliographic record
Abstract
Background: O -GlcNAcylation ( O -GlcNAc) is a post-translational modification involved in the stress response. A single pair of enzymes, O -GlcNAc transferase (OGT) and O -GlcNAcase (OGA) controls the O -GlcNAcylation. Due to the contribution of energy-linked metabolites (e.g. glucose, glutamine, etc.) to produce UDP-GlcNAc, the substrate used by OGT, O -GlcNAc is considered as a nutrient sensor. Metabolic sources vary from carbohydrates in utero , to fatty acids after birth then a mix once adult. Yet the link between diet composition and O -GlcNAc has never been explored. Purpose: Evaluate changes in O -GlcNAc levels and regulatory mechanisms throughout development. Methods: Organs were harvested from Wistar rats (n=6-8 for each group) before and after birth (D-1 and D0), in suckling animals (D12), after weaning with a standard (D28) or a carbohydrate free diet (D28F), and adult (D84). O -GlcNAc levels and regulatory enzymes were evaluated by Western blots. Mass spectrometry (MS) was performed to quantify known regulators of O -GlcNAc (n=6-8) and identify cardiac O -GlcNAcylated proteins at D0 and D28 (n=2). Results: O -GlcNAc levels fell after birth in the heart, brain and liver (2.5, 1.5 and 1.3-fold, respectively). Interestingly, while O -GlcNAc levels decrease progressively from D0 to D84 (5.75-fold p<0.05) in the heart, the O -GlcNAc changes are opposite and of much smaller magnitude in liver and brain. Regulatory mechanisms appear to be in accordance in heart with a decrease in OGT (4.5-fold; p<0.05), an increase in OGA (125-fold; p<0.05) expression and decrease in UDP-GlcNAc (3-fold; p<0.05) over time. Yet changes in expression of OGT, OGA and UDP-GlcNAc do not follow O -GlcNAc levels in brain and liver. O -GlcNAc levels are unaffected by weaning diet in any tissues. MS analyses identified changes in cardiac levels of specific O -GlcNAcylated proteins, namely those involved in the energy metabolism, such as ACAT1, which is only O -GlcNAcylated at D0. Conclusion: We demonstrate that O -GlcNAc levels are not linked to dietary intake and are regulated in a time and tissue-specific manner during postnatal development. We have identified by MS proteins with a particular O -GlcNAc signature across the development process suggesting specific role for those proteins.
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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) | 0.001 | 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) | 0.011 | 0.003 |
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".