Effects of fluoxetine administration on neuropeptide Y and orexins in obese Zucker rat hypothalamus
Effects of fluoxetine administration on neuropeptide Y and orexins in obese Zucker rat hypothalamus
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DOI：
10.1038/oby.2002.72
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发表时间：
2002-06-01
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影响因子：
--
通讯作者：
Portillo, MP
中科院分区：
文献类型：
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作者：
Gutiérrez, A;Saracíbar, G;Portillo, MP
目的：本工作的目的是研究神经肽Y（NPY）和食欲素在氟西汀致肥胖Zucker大鼠厌食机制中的潜在参与，评估长期氟西汀治疗对下丘脑几个区域NPY和食欲素免疫染色的影响。 研究方法和程序：雄性肥胖Zucker（fa/fa）大鼠每日给予氟西汀（10 mg/kg腹腔注射），连续2次。几周。对照组给予0.9% NaCl溶液。使用官方分析化学家协会的官方方法评估胴体成分。为了测试氟西汀给药的潜在产热效应，在注射氟西汀或盐水之前 60 分钟以及注射药物或盐水之后 30 分钟每天测量全身耗氧量。对下丘脑弓状核、室旁核以及下丘脑外侧区进行 NPY、食欲素 A 和食欲素 B 免疫染色。使用商业试剂盒进行血清测定。结果：肥胖 Zucker 大鼠长期服用氟西汀会导致体重增加、食物摄入量、脂肪细胞大小、脂肪量和身体蛋白质减少。观察到室旁核 NPY 免疫染色减少，但弓形没有变化。然而，下丘脑外侧区食欲素 A 或食欲素 B 免疫染色的神经细胞数量没有观察到变化。讨论：由于 NPY 在室旁核中的摄食作用，这些结果表明 NPY 而不是食欲素可能参与了氟西汀对肥胖 Zucker 大鼠的厌食作用。
Objective: The aim of this work was to study the potential involvement of neuropeptide Y (NPY) and orexins in the anorexigenic mechanism of fluoxetine in obese Zucker rats, assessing the effects of chronic fluoxetine treatment on NPY and orexin immunostaining in several hypothalamic regions.Research Methods and Procedures: Male obese Zucker (fa/fa) rats were administered fluoxetine (10 mg/kg intraperitoneally) daily for 2 weeks. The control group was administered 0.9% NaCl solution. Carcass composition was assessed using the official methods of the Association of Official Analytical Chemists. To test the potential thermogenic effect of fluoxetine administration, total body oxygen consumption was measured daily for 60 minutes before fluoxetine or saline injection and for 30 minutes after drug or saline injection. Hypothalamic arcuate and paraventricular nuclei, and the lateral hypothalamic area were immunostained for NPY, orexin A, and orexin B. Commercial kits were used for serum determinations.Results: Chronic fluoxetine administration in obese Zucker rats generated a reduction in body weight gain, food in-take, adipocyte size, fat mass, and body protein. A decrease in NPY immunostaining in the paraventricular nucleus, without changes in the arcuate, was observed. However, no changes were observed in the number of neural cells immunostained for orexin A or orexin B in the lateral hypothalamic area.Discussion: Due to the hyperphagic effect of NPY in the paraventricular nucleus, these results suggest that NPY, but not orexins, could be involved in the anorexigenic effect of fluoxetine in obese Zucker rats.