The leptin sensitizer celastrol reduces age‐associated obesity and modulates behavioral rhythms
Bibliographic record
Abstract
The prevalence of obesity increases with age in humans and in rodents. Age-related obesity is characterized by leptin resistance and associated with heightened risk of metabolic disorders. However, the effect of leptin resistance per se has been difficult to disentangle from other effects of aging. Here we demonstrate that celastrol, a natural phytochemical that was previously shown to act as a leptin sensitizer, induces weight loss in aged animals, but not in young controls. Celastrol reduces food intake and lowers fasting glucose without affecting energy expenditure. Unexpectedly, administration of celastrol just before the dark period disrupted circadian rhythms of sleep and activity. This regimen was also associated with loss of lean mass an outcome that would not be desirable in elderly patients. Adjusting the timing of celastrol administration by 12 hr, to the beginning of the light period, avoided interference with circadian rhythms while retaining the reductions in body weight and adiposity. Thus, targeting leptin signaling is an effective strategy to ameliorate age-associated weight gain, and can profoundly impact circadian rhythms.
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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".