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Effects of olanzapine on the elevation of macrophage infiltration and pro-inflammatory cytokine expression in female rats

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posted on 2024-11-16, 07:12 authored by Qingsheng Zhang, Meng He, Chao DengChao Deng, Hongqin Wang, Xu-Feng HuangXu-Feng Huang
The metabolic side-effects of olanzapine have undermined drug compliance and increased concern for this otherwise-effective treatment for schizophrenia. As obesity and type 2 diabetes are associated with low-grade inflammation, and olanzapine-induced weight gain has three typical stages, the current study investigated the inflammatory effects of olanzapine in three treatment stages. Female Sprague-Dawley rats were treated orally with olanzapine (1 mg/kg three times daily) or vehicle for one week, two weeks, and five weeks. Olanzapine significantly increased body weight and white visceral fat deposition in all three treatment stages compared to control. Olanzapine enhanced average adipocyte size and level of macrophage infiltration in white adipose tissue (WAT) compared to control, with levels of macrophage infiltration increased over time. There was a high correlation between adipocyte size and macrophage infiltration rate. Olanzapine also caused increased macrophage infiltration in brown adipose tissue (BAT), but not liver. Additionally, pro-inflammatory cytokines tumor necrosis factor α (TNFα), interleukin (IL)-1β, and IL-6 were upregulated by olanzapine in the hypothalamus, WAT, and BAT compared to control, but not the liver. Finally, plasma triglycerides were elevated by olanzapine compared to control, but not total cholesterol, high density lipoprotein (HDL) or low density lipoprotein (LDL). These findings indicate that olanzapine-induced inflammation and adiposity are closely related, and that peripheral low-grade inflammation develops during olanzapine treatment.

Funding

Schizophrenia: Reversal of atypical antipsychotic drug-induced obesity and its related metabolic disorders

National Health and Medical Research Council

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History

Citation

Zhang, Q., He, M., Deng, C., Wang, H. & Huang, X. (2014). Effects of olanzapine on the elevation of macrophage infiltration and pro-inflammatory cytokine expression in female rats. Journal of Psychopharmacology, 28 (12), 1161-1169.

Journal title

Journal of Psychopharmacology

Volume

28

Issue

12

Pagination

1161-1169

Language

English

RIS ID

93763

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