Corticotropin-Releasing Factor-Overexpressing Mice Exhibit Reduced Neuronal Activation in the Arcuate Nucleus and Food Intake in Response to Fasting
Corticotropin-Releasing Factor-Overexpressing Mice Exhibit Reduced Neuronal Activation in the Arcuate Nucleus and Food Intake in Response to Fasting
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DOI：
10.1210/en.2008-0723
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发表时间：
2009-01-01
期刊：
影响因子：
4.8
通讯作者：
Wang, Lixin
中科院分区：
文献类型：
--
作者：
Stengel, Andreas;Goebel, Miriam;Wang, Lixin
促肾上腺皮质激素释放因子（CRF）过表达（OE）小鼠是一种表现出慢性应激特征的遗传模型。我们研究了慢性CRF过度产生条件下，对食物剥夺引起的低热量挑战的适应性摄食反应是否受损。在CRF-OE和野生型（WT）同窝小鼠沿着中比较了16小时过夜禁食和腹腔注射调节食物摄入的肠道激素对食物摄入的反应，以及脑Fos表达、循环ghrelin水平和非营养餐的胃排空。与WT相比，CRF-OE小鼠ip注射生理盐水后，过夜禁食的30分钟和4小时累积摄食量分别减少47%和44%。然而，在CRF-OE和WT小鼠中，ip胆囊收缩素（3 μ g/kg）诱导的30分钟摄食量减少和ghrelin（300 μ g/kg）诱导的摄食量增加相似。过夜禁食使CRF-OE和WT小鼠的血浆总ghrelin增加到相似的水平，尽管CRF-OE小鼠的非禁食ghrelin水平降低了2倍。与WT小鼠相比，CRF-OE中弓状核禁食诱导的Fos免疫反应细胞数量减少了5.9倍，而在其他下丘脑核团中未观察到显著变化。与此相反，禁食CRF-OE小鼠显示迷走神经背侧运动核中Fos免疫反应细胞数量增加5.6倍，20分钟胃排空增加34%。这些发现表明，持续过量生产的小鼠下丘脑CRF干扰禁食诱导的弓状核神经元的激活和相关的摄食反应。（内分泌学150：153-160，2009）
Corticotropin-releasing factor (CRF) overexpressing (OE) mice are a genetic model that exhibits features of chronic stress. We investigated whether the adaptive feeding response to a hypocaloric challenge induced by food deprivation is impaired under conditions of chronic CRF overproduction. Food intake response to a 16-h overnight fast and ip injection of gut hormones regulating food intake were compared in CRF-OE and wild type (WT) littermate mice along with brain Fos expression, circulating ghrelin levels, and gastric emptying of a nonnutrient meal. CRF-OE mice injected ip with saline showed a 47 and 44% reduction of 30-min and 4-h cumulative food intake response to an overnight fast, respectively, compared with WT. However, the 30-min food intake decrease induced by ip cholecystokinin (3 mu g/kg) and increase by ghrelin (300 mu g/kg) were similar in CRF-OE and WT mice. Overnight fasting increased the plasma total ghrelin to similar levels in CRF-OE and WT mice, although CRF-OE mice had a 2-fold reduction of nonfasting ghrelin levels. The number of Fos-immunoreactive cells induced by fasting in the arcuate nucleus was reduced by 5.9-fold in CRF-OE compared with WT mice whereas no significant changes were observed in other hypothalamic nuclei. In contrast, fasted CRF-OE mice displayed a 5.6-fold increase in Fos-immunoreactive cell number in the dorsal motor nucleus of the vagus nerve and a 34% increase in 20-min gastric emptying. These findings indicate that sustained overproduction of hypothalamic CRF in mice interferes with fasting-induced activation of arcuate nucleus neurons and the related hyperphagic response. (Endocrinology 150: 153-160, 2009)