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Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin

Journal Article


Abstract


  • © 2020 The Author(s). 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-γco-activator-1α (PGC-1α) 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. Graphical abstract: [Figure not available: see fulltext.]

Authors


  •   Liu, Xuemei (external author)
  •   Feng, Xiyu (external author)
  •   Deng, Chao
  •   Liu, Lu (external author)
  •   Zeng, Yanping (external author)
  •   Hu, Chang (external author)

Publication Date


  • 2020

Citation


  • Liu, X., Feng, X., Deng, C., Liu, L., Zeng, Y. & Hu, C. (2020). Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin. BMC Pharmacology and Toxicology, 21 (1),

Scopus Eid


  • 2-s2.0-85087417937

Volume


  • 21

Issue


  • 1

Place Of Publication


  • United Kingdom

Abstract


  • © 2020 The Author(s). 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-γco-activator-1α (PGC-1α) 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. Graphical abstract: [Figure not available: see fulltext.]

Authors


  •   Liu, Xuemei (external author)
  •   Feng, Xiyu (external author)
  •   Deng, Chao
  •   Liu, Lu (external author)
  •   Zeng, Yanping (external author)
  •   Hu, Chang (external author)

Publication Date


  • 2020

Citation


  • Liu, X., Feng, X., Deng, C., Liu, L., Zeng, Y. & Hu, C. (2020). Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin. BMC Pharmacology and Toxicology, 21 (1),

Scopus Eid


  • 2-s2.0-85087417937

Volume


  • 21

Issue


  • 1

Place Of Publication


  • United Kingdom