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Olanzapine- induced metabolic syndrome pathogenesis: Hypothalamic “leptin resistance” or “pomc resistance”?

Published online by Cambridge University Press:  13 August 2021

F. Veneziani ,
M. Zezza ,
A. Marakhovskaia  and
J.M. Beaulieu
F. Veneziani*
Affiliation:
Pharmacology And Toxicology, University of Toronto, Toronto, Canada
M. Zezza
Affiliation:
School Of Medicine And Surgery, University of Bari, Bari, Italy
A. Marakhovskaia
Affiliation:
Pharmacology And Toxicology, University of Toronto, Toronto, Canada
J.M. Beaulieu
Affiliation:
Pharmacology And Toxicology, University of Toronto, Toronto, Canada
*
*Corresponding author.

Abstract

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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.

Keywords

Translational medicineMetabolic syndromeHypothalamic RNAseq analysisPsychopharmacology
Type
Abstract
Information
European Psychiatry , Volume 64 , Special Issue S1: Abstracts of the 29th European Congress of Psychiatry , April 2021 , pp. S149 - S150
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of the European Psychiatric Association
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