Activation of VEGFR3 and MLC2 are Critical for GLP-2 Enhancement of Chylomicron Transport
Bibliographic record
Abstract
Background and Aims: A significant proportion of absorbed dietary triglycerides (TGs) remain in various intracellular and extracellular intestinal compartments for many hours after fat ingestion, including in the lymphatic circulation. TGs retained in the intestine or lymphatics can be mobilized by the gut peptide glucagon-like peptide 2 (GLP-2) and other stimuli. Our previous published data demonstrated that GLP-2 enhances lymph flow by acting distal to the enterocyte, specifically by enhancing lacteal contractility, in an enteric nervous system-dependent fashion. The objective of the present study was to further explore various intermediates in the signaling pathway whereby GLP-2 enhances mesenteric lymph flow. In this study we focused on the roles of vascular endothelial growth factor receptor 3 (VEGFR3) and myosin light chain 2 (MLC2), known to play important roles in lymphangiogenesis and lymphatic contractility, respectively. Methods: A rat lymph fistula model was utilized in this study. An intraduodenal lipid bolus was applied to the rats 5 hours before the following intraperitoneal (i.p.) administrations: 1) saline (placebo), 2) GLP-2, 3) GLP-2 + MAZ-51 (a VEGFR3 inhibitor), 4) GLP-2 + SAR131675 (a second VEGFR3 inhibitor), 5) GLP-2 + ML-7 (a MLCK inhibitor). Lymph flow and TG output were assessed for 60 minutes after the i.p. administrations. In another set of animals, post-i.p. administration, tissue samples were collected to quantify VEGFR3 and MLC2 activation (via phosphorylation). Results: We showed that GLP-2 treatment acutely activated VEGFR3 and MLC2, and that inhibition of VEGFR3 (via MAZ-51/SAR131675) and MLC2 (via ML-7) abolished GLP-2-induced lymph flow and TG output. Furthermore, VEGFR3 inhibition blocked MLC2 activation. Conclusion: Our data suggest that the activation of VEGFR3 and MLC2 play critical roles in GLP-2's enhancement of chylomicron secretion and that VEGFR3 activation is an important intermediary step in GLP-2's activation of MLC2.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".