Antagonistic effects of mineralocorticoid receptor (MR) blockade on the vascular reactivity of male and female leptinsensitized mice
Bibliographic record
Abstract
Leptin is an adipocyte‐derived hormone secreted in excess in obesity. Due to its ability to increase sympathetic tone, and aldosterone (Aldo) levels, leptin is viewed as a key factor involved in obesity‐related cardiovascular disease (CVD). Females secrete 4 times more leptin than males. Whether females are more sensitive to CVD than males is unknown. We hypothesize that excessive leptin levels trigger an increased Aldo secretion and exaggerated CVD in females. To test this hypothesis we analyzed the cardiovascular phenotype of mice hypersensistive to leptin due to the deletion of PTP1B, a molecular brake on leptin signaling. Irrespective of genotypes, leptin levels were 4 times higher in females. Aldo levels were increased in females and further enhanced with the deletion of PTP1B. Sex and genotype synergistically increases adrenals weight and Aldo synthase expression without effects on angiotensin II levels. Although PTP1B deficiency similarly increases blood pressure in both sexes, it only triggers an endothelial dysfunction in females that was restored by MR blockade. Vascular contractility to phenylephrine, reduced in KO males, was not affected in KO females. MR blockade restored it in males and reduced it in females. This suggests that females are more sensitive to leptin‐mediated CVD than males but also that MR antagonists have sex‐specific effects justifying the need for gender‐based therapy.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".