Physical activity protects NLRP3 inflammasome-associated coronary vascular dysfunction in obese mice
Bibliographic record
Abstract
Activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome mediates the release of pro-inflammatory cytokine interleukin (IL)-1β and thereby plays a pivotal role in the inflammatory response in vascular pathology. An active lifestyle has beneficial effects on inflammation-associated vascular dysfunction in obesity. However, it remains unclear how physical activity regulates NLRP3 inflammasome-mediated vascular dysfunction in obesity. Therefore, we explored the protective effect of physical activity on NLRP3 inflammasome-associated vascular dysfunction in mouse hearts, and the potential underlying mechanisms. C57BL/6J male mice were randomly divided into four groups: (1) control low-fat diet (LF-SED), (2) LF diet with free access to a voluntary running wheel (LF-RUN), (3) high-fat diet (HF-SED; 45% of calories from fat), and (4) HF-RUN. We examined NLRP3 inflammasome-related signaling pathways, nitric oxide (NO) signaling, and oxidative stress in coronary arterioles to test effects of HFD and physical activity. Voluntary running reduced NLRP3 inflammasome and its downstream effects, caspase-1 and IL-1β in coronary arteriole endothelium of obese mice in immunofluorescence staining. HF-RUN attenuated HFD-dependent endothelial NO synthase (eNOS) reduction and thus increased NO production compared to HF-SED. HFD elevated intracellular superoxide production in coronary arterioles while voluntary running ameliorated oxidative stress. Our findings provide the first evidence that voluntary running attenuates endothelial NLRP3 inflammasome activation in coronary arterioles of HFD feeding mice. Results further suggest that voluntary running improves obesity-induced vascular dysfunction by preserved NO bioavailability via restored expression of eNOS and reduced oxidative stress.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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".