Role of FoxO within the microvasculature of the skeletal muscle in diet‐induced obesity
Bibliographic record
Abstract
Obesity has emerged as a growing worldwide epidemic. Excessive accumulation of fat alters the adipose tissue as well as the peripheral tissues. In particular obesity induces capillary rarefaction in the skeletal muscle. We recently found that Forkhead box O1 (FoxO1) is an angiostatic factor in the endothelium of the skeletal muscle. Here we aim to study the role of endothelial FoxO1 during diet‐induced obesity (DIO). A significant reduction in capillary to fibre ratio and an increased expression of FoxO1 were observed in the skeletal muscle of high fat‐fed C57Bl6 mice (58% vs. 6% kCal fat for 14 weeks). By knocking‐down FoxO, we identified thrombospondin1, BMP and activin membrane‐bound inhibitor and soluble frizzled‐related protein 1 as FoxO targets in murine microvascular endothelial cells (EC). The expression of these genes also was altered in the muscles of the DIO mice, consistent with the increase in FoxO1 protein. To further study the role of FoxOs, DIO was induced in mice with EC‐directed deletion of FoxO1,3,4 proteins (ΔFoxO; MxCre+:FoxO1,3,4L/L). After 8 weeks, DIO induced a significant increase in weight gain in both wild‐type and ΔFoxO mice. After 14 weeks, we will characterize the metabolic alterations and the changes in the skeletal muscle microenvironment. Our work will determine the role that endothelial FoxO plays in promoting obesity‐induced capillary rarefaction.
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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 | 0.000 | 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) | 0.001 | 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".