University of Wollongong
Browse

Time-dependent changes and potential mechanisms of glucose-lipid metabolic disorders associated with chronic clozapine or olanzapine treatment in rats

Download (3.53 MB)
journal contribution
posted on 2024-11-16, 03:17 authored by Xuemei Liu, Zhixiang Wu, Jiamei LianJiamei Lian, Chang-Hua Hu, Xu-Feng HuangXu-Feng Huang, Chao DengChao Deng
Chronic treatment with second-generation antipsychotic drugs (SGAs) has been associated with an increased risk of metabolic syndrome. To evaluate the longitudinal changes in glucose-lipid homeostasis after SGA use, we studied the time-dependent effects of olanzapine (OLZ) (3 mg/kg, b.i.d.) or clozapine (CLZ) (20 mg/kg, b.i.d.) treatment on metabolic profiles for 9 weeks in rats. Although only OLZ significantly increased body weight in rats, both OLZ and CLZ elevated blood lipid levels. Chronic OLZ treatment induced significant weight gain leading to a higher fasting insulin level and impaired glucose tolerance, whereas CLZ lowered fasting insulin levels and impaired glucose tolerance independent of weight gain. Treatment with both drugs deranged AKT/GSK phosphorylation and up-regulated muscarinic M3 receptors in the rats' livers. Consistent with an elevation in lipid levels, both OLZ and CLZ significantly increased the protein levels of nuclear sterol regulatory element-binding proteins (SREBPs) in the liver, which was associated with improvement in hepatic histamine H1R. However, enhanced carbohydrate response element binding protein (ChREBP) signalling was observed in only CLZ-treated rats. These results suggest that SGA-induced glucose-lipid metabolic disturbances could be independent of weight gain, possibly through activation of SREBP/ChREBP in the liver.

Funding

Roles of muscarinic M3 receptors in antipsychotic-induced metabolic side-effects: prevention and treatment of antipsychotic-induced insulin dysregulation

National Health and Medical Research Council

Find out more...

History

Citation

Liu, X., Wu, Z., Lian, J., Hu, C., Huang, X. & Deng, C. (2017). Time-dependent changes and potential mechanisms of glucose-lipid metabolic disorders associated with chronic clozapine or olanzapine treatment in rats. Scientific Reports, 7 2762-1-2762-13.

Journal title

Scientific Reports

Volume

7

Issue

1

Language

English

RIS ID

114766

Usage metrics

    Categories

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC