Blocking the urotensin II receptor pathway ameliorates the metabolic syndrome and improves cardiac function in obese mice
Bibliographic record
Abstract
The metabolic syndrome is defined by the presence of hyperlipidemia, obesity, hypertension, and diabetes. The syndrome is associated with significant cardiovascular morbidity and mortality. The aim of the present study was to determine the role of the vasoactive peptide urotensin II (UII) in the pathogenesis of the metabolic syndrome. We used obese mice (ob/ob) to determine the effect of UII receptor (UT) blockage on the different facets of the metabolic syndrome with special emphasis on cardiac function. Our data demonstrate a significant increase in UII and UT expression in the myocardium of obese mice accompanied by a significant decrease in sarco/endoplasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) expression, as well as intracellular Na(+) and Ca(2+) compared with wild-type mice (P<0.05). Treatment of ob/ob mice with the UII receptor antagonist SB657510 significantly improved glucose levels, blood pressure, hyperlipidemia, expression of myocardial SERCA2a, intracellular Na(+) and Ca(2+) and cardiac function in association with a decrease in weight gain, and mammalian target of rapamycin (mTOR) and sodium/hydrogen exchanger 1 (NHE-1) protein expression compared with vehicle (P<0.05). These findings demonstrate an important role for UII in the pathogenesis of the metabolic syndrome and suggest that the use of UT receptor antagonists may provide a new therapeutic tool for the treatment of this syndrome.
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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 | 0.002 | 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 | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".