Endocannabinoid signaling is a critical link between circadian desynchronization and metabolic dysfunction
Bibliographic record
Abstract
It is well documented that disruption of circadian rhythms can cause metabolic dysregulation, but the specific mechanisms involved remain unclear. Our findings demonstrate that the negative metabolic effects of environmental circadian desynchronization (ECD) are dependent upon the cannabinoid receptor 1 (CB1r). The endocannabinoid system has not previously been implicated in mediating the effects of circadian disruption. We showed that ECD induced a positive correlation between the levels of the endocannabinoids AEA and 2-AG in both plasma and liver. While global CB1r knockout protects against the metabolic effects of ECD, behavioral and physiological response to ECD was strikingly similar between WT and CB1r KO mice and could not account for their distinct metabolic outcomes. Using liver-specific CB1r KO mice, we further specified that the ECD-induced metabolic hormone disruption, but not weight gain, is mediated through liver CB1r signaling. Finally, we showed that ECD upregulated transcription of genes involved in oxidative phosphorylation in the liver of WT, but not liver-specific CB1r KO mice. In summary, ECD led to modular metabolic dysfunction through CB1r signaling in multiple tissues, with the liver playing a critical role.
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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) | 0.002 | 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".