Leptin induces interleukin‐1β release from rat microglial cells through a caspase 1 independent mechanism
Bibliographic record
Abstract
Leptin regulates energy balance by suppressing appetite and increasing energy expenditure through actions in the hypothalamus. Recently we demonstrated that the effects of leptin are, at least in part, mediated by the release of interleukin (IL)-1beta in the brain. Microglia constitute the major source of IL-1beta in the brain but it is not known whether these cells express leptin receptors, or respond to leptin to produce IL-1beta. Using RT-PCR and immunocytochemistry, we demonstrate that primary rat microglial cells express the short (non-signalling) and long (signalling) isoforms of the leptin receptors (Ob-R)s. Immunoassays performed on cell medium collected 24 h after leptin treatment (0.01-10 microg/mL) demonstrated a dose-dependent production and release of IL-1beta and its endogenously occurring receptor antagonist IL-1RA. In addition leptin-induced IL-1beta release occurs via a signal transducer and activator of transcription 3 (STAT3)-dependent mechanism. Western blot analysis demonstrated that leptin induced the synthesis of pro-IL-1beta in microglial cells and the release of mature 17 kDa isoform into the culture medium. Leptin-induced IL-1beta release was neither inhibited by the pan-caspase inhibitor BOC-D-FMK, nor by the caspase 1 inhibitor Ac-YVAD-CHO indicating that IL-1 cleavage is independent of caspase activity. These results confirm our earlier observations in vivo and demonstrate that microglia are an important source of IL-1beta in the brain in response to leptin.
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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 | 0.000 |
| 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".