Abstract 531: Sex Differences In The Metabolic Switch From Fasting To Refeeding In The Murine Jejunum
Bibliographic record
Abstract
Introduction: The small intestine receives hormonal and neuronal stimuli to ensure sufficient nutrient absorption to fuel the body. Insulin resistance promotes aberrant dietary fat delivery into circulation, increasing the risk of cardiovascular disease. The mechanisms underlying the loss of controlled dietary fat delivery during metabolic disease are unclear. We aimed to characterize the metabolic pathways engaged in the small intestine in the transition from fasting to refeeding states in both male and female mice. Methods: Eight- to twelve-week-old male and female mice fasted for 24 hours. Half of the mice were euthanized in the fasted state, and the remaining half were euthanized after a 4-hour refeeding period (Teklad Global 19% Protein Extruded Diet). Gene expression and pathway analyses in jejunal samples were determined using Nanostring. Results: In male and female mice, refeeding significantly upregulated pathways in amino acid synthesis, mitochondrial respiration, and proto-oncogene Myc signalling compared to fasting. Refeeding significantly downregulated glycolysis, and both mitogen-activated MAPK and PI3K signalling pathways compared to fasting. Interestingly, in males refeeding significantly upregulated AMPK, mTOR, and autophagy, whereas conversely in female mice, refeeding downregulated these pathways. Surprisingly, fatty acid synthesis and fatty acid oxidation pathways were unchanged by the nutritional state in males, but in females, both pathways were significantly downregulated with refeeding compared to fasting. In female mice, refeeding significantly reduced small intestinal length compared to fasting, whereas intestinal length was unchanged in male mice. Conclusions: Metabolic pathways well-characterized in the liver are often mechanistically extrapolated to the gut. We have begun to uncover the jejunal gene expression changes regulated by nutrient availability in male and female mice. Identifying how high-fat feeding dysregulates these pathways will help further elucidate the mechanism underlying the over-production of intestinally-derived lipoproteins in metabolic disease.
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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 | 0.001 |
| Bibliometrics | 0.001 | 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) | 0.004 | 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".