Olanzapine- induced metabolic syndrome pathogenesis: Hypothalamic “leptin resistance” or “pomc resistance”?
Bibliographic record
Abstract
Introduction Olanzapine (OL) represents one of the main chooses for the treatment of psychosis. However, OL increase the risk of metabolic syndrome (MS). Previous literature proposes the “Leptin resistance” as a possible hypothalamic pathogenesis of OL induced MS because of the occurrence of weight gain with increased Leptin blood level. Objectives The aim of our study is to investigate in a murine model of full-MS phenotype induced by Olanzapine the hypothalamic gene expression of the pathways involved in Leptin receptor signalling to clarify if a Leptin resistance occurs. Methods For the experiment C57BL/6Jfemale mice are used.The OL group (n=15) received pure Olanzapine compounded into chow (54 mg/kg of diet). The vehicle group (n=15)is fed with the same chow without OL. Weight gain is measured every 5 days. After 4 weeks of treatment, mice are sacrificed by rapid cervical dislocation. Blood is collected for Glucose, Insulin and Leptin evaluation. Hypothalamus is dissected and RNA-seq is performed. Results The OL group shows a significantweight gain compared to Control (p= 0.02). Likewise blood glucose, Insulin and Leptin levels appear increased (p= 0,0089, p= 0,01, p= 0,0012). From the analysis of RNA-seq hypothalamic differentially expressed genes the anorexigenic POMC pathway downstream to the Leptin Receptor shows a 4-fold increased compared to control. Conclusions In our study the “Leptin resistance” involvement in OL induced MS is not confirmed. In fact, although there is an increase in blood Leptin, the expression of Leptin receptor downstream pathways shows a significant increase. This could suggest a possible “POMC resistance” mechanism for OL induced MS. Disclosure No significant relationships.
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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) | 0.001 | 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".