Intermittent Fasting with a High Fat Diet Reveals the Contribution of Mitochondrial Free Radicals to the Endothelium‐Dependent Relaxation of Mouse Aorta
Bibliographic record
Abstract
Obesity leads to endothelial dysfunction, promoting age‐related cardiovascular diseases. In mice, a high fat diet (HFD) impairs endothelial function, while caloric restriction slows age‐dependent endothelial dysfunction and increases lifespan. Whether intermittent fasting (IF) influences endothelial function is unknown. Three‐month old C57BL6 mice were fed ad libitum (AL) or every other day (IF) either a regular diet (RD) or a HFD for 16 weeks. Caloric intake was similar in mice fed a RD either AL or in IF; however, RD‐IF prevented body weight gain (p<.05), improved glucose tolerance and insulin sensitivity (p<.05). As expected, HFD‐AL increased caloric intake (+27 %), body weight (+7 g), adipose tissue and liver weight (2 fold), glucose intolerance and insulin resistance (p<.05). Combining HFD and IF reduced by 50 % the rise in caloric intake compared to HFD‐AL (p<.05), fully prevented HFD‐induced gain in body weight, kept optimal (equal to RD‐IF) glucose tolerance, and normalized insulin sensitivity (p<.05). Acetylcholine (Ach)‐induced relaxation was measured in isolated aortic rings. Ach‐induced maximal relaxation (Emax, see Table) was increased in HDF‐AL mice (p<.05) due to a compensatory increase in eNOS activity. IF tended to ameliorate Emax (p=.06), irrespectively of the diet and without changing eNOS activity. In the 4 groups, TEMPOL (SOD mimetic) led to higher (p<.05) vascular sensitivity and Emax to Ach. Interestingly, mitoTEMPO targeting mitochondria, reduced (p<.05) endothelium‐dependent relaxation in HFD‐IF fed mice only, revealing the contribution of mitochondrial free radicals to the endothelium‐dependent relaxation of mouse aorta. Emax (%) RD‐AL HFD‐AL RD‐IF HFD‐IF Control 52 ± 6 78 ± 4 * 68 ± 5 68 ± 7 L‐NNA (eNOS inhibitor) 22 ± 7 $ 41 ± 10 $ 33 ± 10 $ 31 ± 13 $ TEMPOL (SOD mimetic) 95 ± 2 $ 90 ± 3 90 ± 4 $ 85 ± 5 mitoTEMPO (mitochondrial SOD2 mimetic) 66 ± 12 70 ± 6 66 ± 8 46 ± 8 $ data are presented as mean ± SEM; * p<0.05 vs. RD‐AL; $ p<0.05 vs. Control.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".