1615-P: The Peripheral and Central Cross Talk Mediated by Adipose MIF—A Novel Mechanism of Hyperphagia following Olanzapine Treatment
Why this work is in the frame
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Bibliographic record
Abstract
Olanzapine is one of the first-line antipsychotic medications but it usually induces metabolic side effects, characterized by obesity. We previously indicated that olanzapine leads to hyperphagia through the effects of a proinflammatory cytokine, macrophage migration inhibitory factor (MIF) in the hypothalamus. However, whether olanzapine's upregulated peripheral MIF could affect the central mechanism is currently unknown. Our present study found that olanzapine increases ectopic expression of dopamine receptor 1 (DRD1) in adipocytes which relatively upregulates MIF expression and release through a PKA/CREB signaling pathway. In global MIF knockout mice, MIF accumulation appears in the hypothalamus following peripheral injection of recombinant MIF proteins, suggesting that peripheral MIF indeed travels to the hypothalamus. Mif Lung Tg mice (MIF overexpression in the lung) with increased circulating MIF levels had hyperphagia and activation of the CaMKKβ/AMPK/AgRP signaling pathway in the hypothalamus. Overall, our study for the first time proved that adipose-derived MIF is a crucial factor in regulating metabolic side effects induced by olanzapine. Disclosure X.Chen: None. Y.Huang: None. Y.Qi: None. L.Chen: None. L.Li: None. P.Gao: None. D.Cui: None. D.Qi: None. Funding National Sciences and Engineering Research Council of Canada (RGPIN-2017-04542); Canadian Institutes of Health Research (PJT-156116); China Scholarship Council (202106230212)
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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 | 0.000 | 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 it