Dopaminergic agonists normalize elevated hypothalamic neuropeptide Y and corticotropin-releasing hormone, body weight gain, and hyperglycemia in ob/ob mice
Dopaminergic agonists normalize elevated hypothalamic neuropeptide Y and corticotropin-releasing hormone, body weight gain, and hyperglycemia in ob/ob mice
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DOI：
10.1159/000054522
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发表时间：
2000-01-01
影响因子：
4.1
通讯作者：
Cincotta, AH
中科院分区：
文献类型：
--
作者：
Bina, KG;Cincotta, AH
下丘脑神经肽Y（NPV）和促肾上腺皮质激素释放激素（CRH）影响进食和血糖、胰岛素、游离脂肪酸和甘油三酯水平。用多巴胺受体D-1/D-2激动剂治疗遗传性肥胖的ob/ob小鼠，使摄食过多、体重增加、高血糖症和高脂血症正常化。因此，我们研究了在ob/ob小鼠的离散下丘脑核团中NPY和CRH免疫反应性的水平是否改变，以及多巴胺能治疗是否逆转这种改变。雌性ob/ob小鼠在光发作后1小时每天分别用D-1/D-2激动剂SKF-38393（20 mg/kg）和溴隐亭（15 mg/kg）或溶剂处理2周。这样的治疗，同时正常化体重增加和高血糖症，也显着降低升高的NPV免疫反应性在视交叉上核（39%），膝状体间（43%），室旁核（PVN; 31%），弓状核（41%）在肥胖小鼠中观察到的水平。与肥胖对照组相比，这种治疗还导致PVN和背内侧下丘脑中CRH水平下降45-50%至瘦小鼠中观察到的水平。综上所述，这些发现表明，多巴胺能D-1/D-2受体共激活可能会改善肥胖症/肥胖小鼠，在parr，通过正常化升高水平的NPY和CRH。版权所有（C）2000 S. Karger AG，巴塞尔。
Hypothalamic neuropeptide \Y (NPV) and corticotropin-releasing hormone (CRH) influence feeding and levels of plasma glucose, insulin, free fatty acids, and triglycerides. Treatment of genetically obese, ob/ob mice, with dopamine receptor D-1/D-2 agonists normalizes hyperphagia, body weight gain, hyperglycemia, and hyperlipidemia. We therefore examined whether levels of NPY and CRH immunoreactivity in discrete hypothalamic nuclei are altered in ob/ob mice, and whether dopaminergic treatment reverses this alteration. Female ob/ob mice were treated daily at 1 h after light onset with the D-1/D-2 agonists, SKF-38393 (20 mg/kg) and bromocriptine (15 mg/kg), respectively or vehicle for 2 weeks. Such treatment, while normalizing body weight gain and hyperglycemia, also significantly reduced elevated NPV immunoreactivity in the suprachiasmatic (by 39%), intergeniculate (by 43%), paraventricular (PVN; by 31%), and arcuate (by 41%) nuclei in obese mice to levels observed in lean mice. This treatment also caused a 45-50% decline in levels of CRH in the PVN and dorsomedial hypothalamus compared to obese controls to levels observed in lean mice. Taken together, these findings suggest that dopaminergic D-1/D-2 receptor coactivation may improve hyperphagia, hyperglycemia, and obesity in the ob/ob mouse, in parr, by normalizing elevated levels of both NPY and CRH. Copyright (C) 2000 S. Karger AG, Basel.