Abstract 661: Tie2 Deficiency Leads to Lymphatic Defects and Resistance to High-fat Diet Induced Obesity
Bibliographic record
Abstract
The Angiopoietin-Tie2 signaling pathway is a critical regulator in vascular development, with conventional Ang1 or Tie2 knockout mice dying in utero with vascular defects. While the role of this pathway in vascular development is apparent, the severity of developmental phenotypes makes it difficult to study Tie2 in vivo. Here, we investigate the functional role of Tie2 in embryonic as well as adult mice using inducible knockout mouse models (Tie2 cKO). Tie2 inactivation at early stages of gestation (E12.5 or E14.5), which coincides with the initial stages of lymphatic development and remodeling, resulted in severe subcutaneous edema in E16.5 and altered lymphatic vessel morphology in the dermis of E17.5. These results indicate the important role of Tie2 in lymphatic development. In contrast, Tie2 inactivation at later stages (E18.5-P0) resulted in the birth of viable pups, indicating that Tie2 is dispensable after embryonic development. Adult male Tie2 cKO mice have similar blood glucose, glucose tolerance, and plasma lipids compared to controls. However, body weight of Tie2 cKO mice upon high-fat diet feeding was lower than that of control mice (47.5+-0.6g (control) vs. 38.0+-2.0g (Tie2 cKO), p<0.01 (4weeks after high-fat diet feeding)). Although plasma lipids (cholesterol and triglyceride) in control and Tie2 cKO mice were similar after high-fat diet feeding, mRNA expression of TNFa (100+-14% (control) vs. 40+-1.4% (Tie2 cKO), p<0.05) and F4/80 (100+-13% (control) vs. 53+-7.3% (Tie2 cKO), p<0.05) in epididymal fat were reduced in Tie2 cKO mice. Our data show that Tie2 plays an import role in lymphatic development during embryogenesis and that Tie2 signaling is also important for adipose tissue growth in adult mice.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".