Direct effects of leptin on size and extracellular matrix components of human pediatric ventricular myocytes
Bibliographic record
Abstract
OBJECTIVE: There is a well-documented association between obesity and heart failure although the mechanistic basis for this correlation is unclear. Both extracellular matrix remodeling and left ventricular hypertrophy are well-defined components of remodeling in heart failure, and here we further investigate the role of leptin, the obese gene product, on these parameters. METHODS: We used primary human pediatric ventricular cardiomyocytes combined with gelatin zymography, quantitative PCR analysis, proline and leucine incorporation assays, and investigation of kinase activation by Western blotting. RESULTS: We show using gelatin zymography that leptin dose-dependently (0-60 nM) increased proteolytic activity at approximately 72 kDa. Accordingly, upon quantitative PCR analysis we found that leptin increased expression of matrix metalloproteinase-2 (MMP-2). Leptin also caused an increase in collagen type III and IV mRNA expression and a decrease in collagen type I mRNA expression. This was reflected in no significant change in total collagen synthesis, measured by [3H]proline incorporation, in response to leptin. A statistically significant increase in cell size, [3H]leucine incorporation, and expression of well-characterized markers of cardiac hypertrophy, namely cardiac alpha-actin and myosin light chain, were observed in response to leptin. We demonstrate activation of Janus-activated kinase and mitogen-activated protein kinase pathways by leptin, and using pharmacological inhibitors we show that these signaling pathways play a role in mediating the effects of leptin. CONCLUSIONS: Our findings show that leptin regulates cell size, stimulates MMP-2 expression, and alters the profile, but not the total content, of collagen in human cardiomyocytes. This indicates the potential for altered leptin sensitivity to directly regulate cardiac remodeling in obesity.
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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) | 0.000 | 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) | 0.001 | 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 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".