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

Abstract 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.)...

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Autores principales:	Xuemei Liu, Zhixiang Wu, Jiamei Lian, Chang-Hua Hu, Xu-Feng Huang, Chao Deng
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d44ba3620fcd44e58ea44ad0872f6987
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spelling	oai:doaj.org-article:d44ba3620fcd44e58ea44ad0872f69872021-12-02T11:52:30ZTime-dependent changes and potential mechanisms of glucose-lipid metabolic disorders associated with chronic clozapine or olanzapine treatment in rats10.1038/s41598-017-02884-w2045-2322https://doaj.org/article/d44ba3620fcd44e58ea44ad0872f69872017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02884-whttps://doaj.org/toc/2045-2322Abstract 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.Xuemei LiuZhixiang WuJiamei LianChang-Hua HuXu-Feng HuangChao DengNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xuemei Liu Zhixiang Wu Jiamei Lian Chang-Hua Hu Xu-Feng Huang Chao Deng Time-dependent changes and potential mechanisms of glucose-lipid metabolic disorders associated with chronic clozapine or olanzapine treatment in rats
description	Abstract 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.
format	article
author	Xuemei Liu Zhixiang Wu Jiamei Lian Chang-Hua Hu Xu-Feng Huang Chao Deng
author_facet	Xuemei Liu Zhixiang Wu Jiamei Lian Chang-Hua Hu Xu-Feng Huang Chao Deng
author_sort	Xuemei Liu
title	Time-dependent changes and potential mechanisms of glucose-lipid metabolic disorders associated with chronic clozapine or olanzapine treatment in rats
title_short	Time-dependent changes and potential mechanisms of glucose-lipid metabolic disorders associated with chronic clozapine or olanzapine treatment in rats
title_full	Time-dependent changes and potential mechanisms of glucose-lipid metabolic disorders associated with chronic clozapine or olanzapine treatment in rats
title_fullStr	Time-dependent changes and potential mechanisms of glucose-lipid metabolic disorders associated with chronic clozapine or olanzapine treatment in rats
title_full_unstemmed	Time-dependent changes and potential mechanisms of glucose-lipid metabolic disorders associated with chronic clozapine or olanzapine treatment in rats
title_sort	time-dependent changes and potential mechanisms of glucose-lipid metabolic disorders associated with chronic clozapine or olanzapine treatment in rats
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d44ba3620fcd44e58ea44ad0872f6987
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Time-dependent changes and potential mechanisms of glucose-lipid metabolic disorders associated with chronic clozapine or olanzapine treatment in rats

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