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Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin.
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ABSTRACT: Background
Prescription of second-generation antipsychotic drugs (SGAs) to childhood/adolescent has exponentially increased in recent years, which was associated with the greater risk of significant weight gain and dyslipidemia. Statin is considered a potential preventive and treatment approach for reducing SGA-induced weight gain and dyslipidemia in schizophrenia patients. However, the effect of statin treatment in children and adolescents with SGA-induced dyslipidemia is not clearly demonstrated.Methods
To investigate the efficacy of statin interventions for reversing SGA-induced dyslipidemia, young Sprague Dawley rats were treated orally with either olanzapine (1.0?mg/kg, t.i.d.), simvastatin (3.0?mg/kg, t.i.d.), olanzapine plus simvastatin (O?+?S), or vehicle (control) for 5?weeks.Results
Olanzapine treatment increased weight gain, food intake and feeding efficiency compared to the control, while O?+?S co-treatment significantly reversed body weight gain but without significant effects on food intake. Moreover, olanzapine treatment induced a slight but significant reduction in body temperature, with a decrease in locomotor activity. Fasting plasma glucose, triglycerides (TG), and total cholesterol (TC) levels were markedly elevated in the olanzapine-only group, whereas O?+?S co-treatment significantly ameliorated these changes. Pronounced activation of lipogenic gene expression in the liver and down-regulated expression of uncoupling protein-1 (UCP1) and peroxisome-proliferator-activated receptor-? co-activator-1? (PGC-1?) in brown adipose tissue (BAT) was observed in the olanzapine-only group. Interestingly, these protein changes could be reversed by co-treatment with O?+?B.Conclusions
Simvastatin is effective in ameliorating TC and TG elevated by olanzapine. Modulation of BAT activity by statins could be a partial mechanism in reducing metabolic side effects caused by SGAs in child and adolescent patients.
SUBMITTER: Liu X
PROVIDER: S-EPMC7325271 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin.
BMC pharmacology & toxicology 20200630 1
<h4>Background</h4>Prescription of second-generation antipsychotic drugs (SGAs) to childhood/adolescent has exponentially increased in recent years, which was associated with the greater risk of significant weight gain and dyslipidemia. Statin is considered a potential preventive and treatment approach for reducing SGA-induced weight gain and dyslipidemia in schizophrenia patients. However, the effect of statin treatment in children and adolescents with SGA-induced dyslipidemia is not clearly de ...[more]