Olanzapine Induced Dysmetabolic Changes Involving Tissue Chromium Mobilization in Female Rats

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.

Early Lipid Metabolic Effects of the Anti-Psychotic Drug Olanzapine on Weight Gain and the Associated Gene Expression

“…A previous study has showed that oral gavage (2mg/kg) of olanzapine in rats induced significant weight gain over control beginning at day 5. 30 In addition, chronic olanzapine treatment did not significantly increase liver mass or visceral adiposity in our study. A number of rodent studies have reported that chronic olanzapine treatment does not increase triglyceride and cholesterol plasma levels or induce weight gain independent increases in triglyceride levels.…”

“…In other reports, different delivery routes (oral gavage and intraperitoneal injection) and higher doses (up to 10 mg/kg) were used. 7 , 30 In future studies we will include various doses and harvest the tissue samples at several time points for comparison. Secondly, the use of animal models of psychiatric disorders may also provide more information.…”

Association of Typical Toxic Heavy Metals with Schizophrenia

“…For example, one study has suggested that Cr can be used as a treatment for psychiatry disease and have a positive impact on the patient’s mood by lowering the functional sensitivity of the serotonin 2A receptor [41]. In Yang’s study, daily intake of Cr supplements can improve the side-effect of anti-schizophrenia drugs such as weight gain and metabolic disorders [42]. Therefore, our results assume that serum Cr concentrations may correlate with antipsychotics; however, whether its concentration is associated with the risk of developing schizophrenia and/or the progress of schizophrenia will require further research.…”

Nanotechnology Approaches for Enhanced CNS Drug Delivery in the Management of Schizophrenia

“…84 Metabolomics can discover untimely biochemical modifications in disorder and lets in developing predictive biomarkers. 85 In fact, metabolomics appears promising for analysing and identifying metabolic functions that describe certain pathological and physiological states. 86 However, and metabolomics biomarkers need to be helpful for analysis, therapeutics and practical evaluation, the discovery of novel drugs and healing efficacy tracking.…”