Sex differences in the intestinal transcriptome and spatial patterns of lipid uptake capacity and intestinal lipid-metabolic gene expression
Bibliographic record
Abstract
The mammalian small intestine expresses three members of the fatty acid binding protein family; Fabp1, Fabp2, and Fabp6 that differ in their spatial expression pattern and ligand binding preference. In vitro studies using recombinant FABPs suggest an important role in lipid uptake and intestinal lipid metabolism, although the in vivo functions remain unclear. Mice genetically altered to lack Fabp2 exhibit a sex-dimorphic response to high fat diet feeding featuring weight gain and fatty liver in males but not females, suggesting that Fabp2 is involved in a sex-dimorphic intestinal metabolic program. We developed a technique for the analysis of sex differences in transcriptome data and applied it to a study of the intestinal transcriptome of chow-fed Fabp2-/- mice. This analysis revealed lipid metabolic pathways that are differentially regulated in male and female Fabp2-/- mice. We next conducted a high fat diet feeding study for the purpose of analyzing the effects of Fabp2 loss on lipid uptake capacity and spatial expression patterns of lipid metabolic genes identified from the transcriptome experiment. Females lacking Fabp2 exhibited an increased capacity for lipid uptake and an increased abundance of Fabp1 mRNA in the proximal intestine. Loss of Fabp2 also caused an increased excretion of total lipids in females compared to males. This suggests that females might be protected from the adverse effects of Fabp2 loss by directing excess lipids towards excretion pathways through an intracellular, Fabp1-mediated mechanism.
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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 | 0.001 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".