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
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
复制标题
DOI：
10.1007/s10571-011-9663-8
复制
发表时间：
2011-06
影响因子：
4
通讯作者：
Ei Sejima;A. Yamauchi;T. Nishioku;M. Koga;Kengo Nakagama;S. Dohgu;K. Futagami;Y. Kataoka
中科院分区：
文献类型：
--
作者：
Ei Sejima;A. Yamauchi;T. Nishioku;M. Koga;Kengo Nakagama;S. Dohgu;K. Futagami;Y. Kataoka
已知奥氮平在精神分裂症患者的结局和药物依从性方面具有优势。然而，与其他抗精神病药物相比，奥氮平具有不良反应，包括体重增加和代谢紊乱的发生率较高。这些不良事件的潜在机制仍然不清楚。雌性大鼠经口给予奥氮平（2 mg/kg）或溶剂，每天一次，持续2周，以确定下丘脑AMP活化蛋白激酶（AMPK）是否介导奥氮平诱导的体重增加和摄食过多。每天和每两天分别评价每只大鼠的体重和摄食量。在药物治疗终止后，我们使用蛋白质印迹分析来测量下丘脑中AMPK和磷酸化AMPK的蛋白质水平。奥氮平显著增加体重和摄食量。奥氮平可显著升高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长期治疗诱导的食欲亢进和体重增加。
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.