107-OR: Brain GLP-1R Is Likely Required for Peripheral Liraglutide Treatment on Stimulating Hepatic FGF21
Bibliographic record
Abstract
Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) are therapeutic agents for Type 2 Diabetes (T2D) and chronic weight management. We reported previously that peripheral GLP-1RA (liraglutide, Lira) administration stimulates hepatic fibroblast growth factor 21 (FGF21) in wild type but not GLP-1R-/- mice, and GLP-1R is not expressed in the liver tissue. Here we aim to determine the underlying mechanisms for such stimulatory effect via organ-organ communications. Firstly, we asked whether acute intraduodenal (i.d.) GLP-1RA administration stimulates hepatic FGF21; and if so, whether the stimulation requires GLP-1R. We revealed that i.d. administration of GLP-1RA in WT mice significantly elevated hepatic Fgf21 levels by 5-fold compared to WT mice received i.d. PBS, whereas such effect was virtually lost in GLP-1R-/- mice. Secondly, we investigated the central role of GLP-1R. We antagonized brain GLP-1R activity via i.c.v. Ex9-39 injection after peripheral Lira treatment in HFD-challenged mice. Mice received peripheral Lira treatment and i.c.v. Exendin 9-39 treatment show impaired stimulatory effect on serum FGF21 compared to the i.c.v. PBS counterpart, suggesting that brain GLP-1R is likely required for peripheral GLP-1RA to stimulate hepatic FGF21. Together, we further demonstrated that peripheral GLP-1RA administration stimulates hepatic FGF21, and revealed that such beneficial effect likely requires brain GLP-1R. Our study will aid the understanding of metabolic hormones and pave the way for determining their underlying mechanisms in metabolic homeostasis Disclosure J. Feng: None. W. Shao: None. T. Jin: None. Funding Canadian Institutes of Health Research (PJT159735) Guarantor: Tianru Jin
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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".