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Olanzapine Induced Dysmetabolic Changes Involving Tissue Chromium Mobilization in Female Rats

1
Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan
2
Department of Family Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan
3
Center for Geriatrics and Gerontology, Taichung Veterans General Hospital, Taichung 407, Taiwan
4
Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan
5
Graduate Institute of Biotechnology, National Chung Hsing University, Taichung 402, Taiwan
6
Department of Pediatrics, Tungs’ Taichung Metro Harbor Hospital, Taichung 435, Taiwan
7
Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 447, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(3), 640; https://doi.org/10.3390/ijms20030640
Received: 7 January 2019 / Revised: 28 January 2019 / Accepted: 30 January 2019 / Published: 1 February 2019
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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Abstract

Atypical antipsychotics, such as olanzapine, are commonly prescribed to patients with schizophrenic symptoms and other psychiatric disorders. However, weight gain and metabolic disturbance cause adverse effects, impair patient compliance and limit clinical utility. Thus, a better understanding of treatment-acquired adverse effects and identification of targets for therapeutic intervention are believed to offer more clinical benefits for patients with schizophrenia. Beyond its nutritional effects, studies have indicated that supplementation of chromium brings about beneficial outcomes against numerous metabolic disorders. In this study, we investigated whether olanzapine-induced weight gain and metabolic disturbance involved chromium dynamic mobilization in a female Sprague-Dawley rat model, and whether a dietary supplement of chromium improved olanzapine-acquired adverse effects. Olanzapine medicated rats experienced weight gain and adiposity, as well as the development of hyperglycemia, hyperinsulinemia, insulin resistance, hyperlipidemia, and inflammation. The olanzapine-induced metabolic disturbance was accompanied by a decrease in hepatic Akt and AMP-activated Protein Kinase (AMPK) actions, as well as an increase in serum interleukin-6 (IL-6), along with tissue chromium depletion. A daily intake of chromium supplements increased tissue chromium levels and thermogenic uncoupling protein-1 (UCP-1) expression in white adipose tissues, as well as improved both post-olanzapine weight gain and metabolic disturbance. Our findings suggest that olanzapine medicated rats showed a disturbance of tissue chromium homeostasis by inducing tissue depletion and urinary excretion. This loss may be an alternative mechanism responsible for olanzapine-induced weight gain and metabolic disturbance. View Full-Text
Keywords: chromium; hyperglycemia; obesity; olanzapine chromium; hyperglycemia; obesity; olanzapine
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Yang, C.-P.; Wang, Y.-Y.; Lin, S.-Y.; Hong, Y.-J.; Liao, K.-Y.; Hsieh, S.-K.; Pan, P.-H.; Chen, C.-J.; Chen, W.-Y. Olanzapine Induced Dysmetabolic Changes Involving Tissue Chromium Mobilization in Female Rats. Int. J. Mol. Sci. 2019, 20, 640.

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