title: Effects of olanzapine on the elevation of macrophage infiltration and pro-inflammatory cytokine expression in female rats.
abstract: 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.
authors.affiliation: Centre for Translational Neuroscience, University of Wollongong, Wollongong, NSW, Australia Illawarra Health and Medical Research Institute, Wollongong, NSW, NSW, Australia.
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Centre for Translational Neuroscience, University of Wollongong, Wollongong, NSW, Australia Illawarra Health and Medical Research Institute, Wollongong, NSW, NSW, Australia.
authors.forename: Meng
authors.initials: M
authors.lastname: He
authors.affiliation: Centre for Translational Neuroscience, University of Wollongong, Wollongong, NSW, Australia Schizophrenia Research Institute, Darlinghurst, NSW, Australia.
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
authors.affiliation: Centre for Translational Neuroscience, University of Wollongong, Wollongong, NSW, Australia Illawarra Health and Medical Research Institute, Wollongong, NSW, NSW, Australia.
authors.forename: Hongqin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Centre for Translational Neuroscience, University of Wollongong, Wollongong, NSW, Australia Schizophrenia Research Institute, Darlinghurst, NSW, Australia xhuang@uowmail.edu.au.
authors.forename: Xu-Feng
authors.initials: XF
authors.lastname: Huang
mesh_terms: D017667:Adipocytes / Q000187:drug effects; D000273:Adipose Tissue / Q000187:drug effects; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001569:Benzodiazepines / Q000009:adverse effects*; D001835:Body Weight / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced*; D050152:Intra-Abdominal Fat / Q000187:drug effects; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D000077152:Olanzapine; D051381:Rats; D014280:Triglycerides / Q000097:blood
chemical_list: D016207:Cytokines; D008074:Lipoproteins; D014280:Triglycerides; D001569:Benzodiazepines; D000077152:Olanzapine
keywords: Antipsychotics; adiposity; inflammation; macrophage infiltration; olanzapine