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A Role for Hypothalamic AMP-Activated Protein Kinase in the Mediation of Hyperphagia and Weight Gain Induced by Chronic Treatment with Olanzapine in Female Rats

机译:下丘脑AMP激活的蛋白激酶在长期服用奥氮平治疗雌性大鼠所致的吞噬和体重增加介导中的作用

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Olanzapine is known to be advantageous with respect to outcome and drug compliance in patients with schizophrenia. However, olanzapine has adverse effects, including a higher incidence of weight gain and metabolic disturbances, when compared with those of other antipsychotic agents. The mechanisms underlying these adverse events remain obscure. Female rats were orally administered olanzapine (2 mg/kg) or vehicle once a day for 2 weeks to ascertain if hypothalamic AMP-activated protein kinase (AMPK) mediates olanzapine-induced weight gain and hyperphagia. Body weight and food intake in each rat were evaluated every day and every two days, respectively. After the termination of drug treatment, we measured the protein levels of AMPK and phosphorylated AMPK in the hypothalamus using western blot analyses. Olanzapine significantly increased body weight and food intake. The phosphorylation levels of AMPK were significantly elevated by olanzapine. These results suggest that activation of hypothalamic AMPK may mediate hyperphagia and weight gain induced by chronic treatment with olanzapine.
机译:已知奥氮平在精神分裂症患者的预后和药物依从性方面是有利的。但是,与其他抗精神病药相比,奥氮平具有不良影响,包括体重增加和代谢紊乱的发生率更高。这些不良事件的潜在机制仍然不清楚。雌性大鼠每天口服奥氮平(2 mg / kg)或赋形剂,持续2周,以确定下丘脑AMP激活的蛋白激酶(AMPK)是否介导奥氮平诱导的体重增加和食欲亢进。每天和每两天分别评估每只大鼠的体重和食物摄入量。药物治疗终止后,我们使用蛋白质印迹分析测量了下丘脑中AMPK和磷酸化AMPK的蛋白质水平。奥氮平可显着增加体重和食物摄入量。奥氮平可显着提高AMPK的磷酸化水平。这些结果表明,下丘脑AMPK的激活可能介导了奥氮平的慢性治疗引起的食欲亢进和体重增加。

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