Abstract 248: Leptin-mediated Cardiovascular Disease Involves Aldosterone in Female Mice and Adolescent Women
Bibliographic record
Abstract
Premenopausal women have a better endothelial function than men but are more sensitive to obesity induced endothelial dysfunction (ED) and more reactive to mineralocorticoid receptor (MR) blockade. Due to its control of sympathetic activity, leptin has been reported to be the link between metabolic and cardiovascular disease (CVD) in men. Whether a similar correlation exists in females that secrete 4 times more leptin than men is unknown. Using a population based study and mice deficient (KO) in protein tyrosine phosphatase 1B (PTP1B), a leptin sensitizer, we tested the hypothesis that leptin mediated CVD involves sex specific mechanisms. Plasma leptin were 4 times higher in female mice (KO F :1648±271 vs KO M : 347±47 pg/ml; p<0.05) indifferently of the genotype (WT F : 2386±765 vs WT M : 375±37 pg/ml; p<0.05). PTP1B deletion increased leptin sensitivity and raised blood pressure (BP) to a similar extent in males and females (124±4 vs 126±4 respectively; WT 102±5 mmHg) but induced ED in females KO only (p<0.01 vs WT and males). Sympathetic tone was assessed by measuring BP response to ganglionic blockade. Leptin sensitized males only exhibit an increased sympathetic tone, but leptin sensitized females only exhibit high plasma aldosterone levels (aldo; KO F :1234±173 vs WT F : 545±71and KO M : 624±70 pg/ml). Both leptin receptor antagonist and MR blockade restored BP in KO females. In vivo and ex vivo (aortic ring) MR blockade restored endothelial function in females KO suggesting direct aldo effects on the vessels. Neither corticosterone, potassium nor angiotensin II was increased in KO females. However aldosterone synthase expression was impressively increased in females KO only. Aldo levels are low in obese leptin receptor deficient females (333±89 pg/ml), and leptin directly stimulates aldosterone secretion in glomerulosa cells. In parallel we demonstrated that African American adolescent females secrete 4 times more leptin than males, and established a correlation between leptin and aldosterone(r=0.464, p=0.011) in female subjects only. These human and animal data suggest that leptin regulates aldo secretion in females. All together these data suggest that obesity mediated CVD is leptin dependent and involves aldo dependent mechanisms in females.
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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 | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.014 | 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".