Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin
Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin
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DOI：
10.1186/s40360-020-00427-0
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发表时间：
2020-06-30
影响因子：
2.9
通讯作者：
Hu, Chang-Hua
中科院分区：
文献类型：
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作者：
Liu, Xuemei;Feng, Xiyu;Hu, Chang-Hua
背景资料：近年来，第二代抗精神病药物（SGAs）在儿童/青少年中的处方呈指数增长，这与体重显著增加和血脂异常的风险增加有关。他汀类药物被认为是一种潜在的预防和治疗方法，可以减少精神分裂症患者中SGA诱导的体重增加和血脂异常。方法：为了研究他汀类药物干预逆转SGA诱导的血脂异常的疗效，年轻的Sprague道利大鼠口服奥氮平（1.0 mg/kg，t.i.d.），辛伐他汀（3.0 mg/kg，t.i.d.），结果：与对照组相比，奥氮平治疗组大鼠体重增加、摄食量和摄食效率增加，而奥氮平+辛伐他汀（O + S）联合治疗组大鼠体重增加明显逆转，但对摄食量无明显影响。此外，奥氮平治疗引起体温轻微但显著降低，自发活动减少。空腹血糖，甘油三酯（TG），总胆固醇（TC）水平显着升高，奥氮平组，而O + S的共同治疗显着改善这些变化。在仅奥氮平组中观察到肝脏中脂肪生成基因表达的显著激活以及棕色脂肪组织（BAT）中解偶联蛋白-1（UCP 1）和过氧化物酶体增殖物激活受体-γ共激活因子-1 α（PGC-1 α）表达的下调。有趣的是，这些蛋白质的变化可以逆转与O + B的共同治疗。结论：辛伐他汀是有效的改善奥氮平升高TC和TG。他汀类药物对BAT活性的调节可能是减少儿童和青少年患者中SGA引起的代谢副作用的部分机制。
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-gamma co-activator-1 alpha (PGC-1 alpha) 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.