Deficits in E2-dependent control of feeding, weight gain, and cholecystokinin satiation in ER-α null mice
Deficits in E2-dependent control of feeding, weight gain, and cholecystokinin satiation in ER-α null mice
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DOI：
10.1210/en.142.11.4751
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发表时间：
2001-11-01
期刊：
影响因子：
4.8
通讯作者：
Ogawa, S
中科院分区：
文献类型：
--
作者：
Geary, N;Asarian, L;Ogawa, S
为了验证经典ER α (ER α)基因表达在E对食物摄入和体重的抑制作用中的作用，我们对野生型（WT）小鼠和ER α零突变（α ERKO）小鼠进行了卵巢切除并给予E2苯甲酸酯（75 pg/d）或对照物。小鼠在9周龄时切除卵巢，此时基因型对食物摄入量和体重没有显著影响。在卵巢切除术后恢复的18 d测试中，与E2处理的WT小鼠相比，运载工具处理的WT小鼠每天的食物摄入量增加，体重增加更多，而E2处理和运载工具处理的aERKO小鼠的食物摄入量和体重增加没有差异。胴体分析显示体脂含量发生平行变化，但水和蛋白质含量没有变化。由于外周胆囊收缩素（CCK）饱足信号系统的效力的增加介导了E2对大鼠摄食的部分影响，因此测试了250杯选择性CCKA受体拮抗剂德伐赛德的影响。在e2处理的WT小鼠中，Devazepide增加了3小时的食物摄入量，但在两组α ERKO小鼠中均无效。此外，腹腔注射4杯/千克CCK-8， E2处理的WT小鼠的孤立束核中表达c-Fos免疫反应性的细胞数量比载药处理的WT小鼠多，而E2在α - ERRO小鼠中没有这种影响。因此，内质网α对于小鼠食物摄入、体重、肥胖和外周CCK饱足信号系统对E2的正常反应是必需的，而内质网β对于上述任何作用都是不足够的。这是首次证实雌激素受体α基因表达参与雌性小鼠摄食行为和体重调节的雌激素调控。
To test the role of gene expression of the classical ER (ER alpha) in the inhibitory effects of E on food intake and body weight, we ovariectomized and administered E2 benzoate (75 pg/d) or vehicle to wild-ty pe (WT) mice and mice with a null mutation of ER alpha (alpha ERKO). Mice were ovariectomized at age 9 wk, at which time there was no significant effect of genotype on food intake or body weight. During an 18-d test after recovery from ovariectomy, vehicle-treated WT mice increased daily food intake and gained more body weight than E2-treated WT mice, whereas food intake and body weight gain were not different in E2- and vehicle-treated aERKO mice. Carcass analysis revealed parallel changes in body lipid content, but not water or protein content. Because an increase in the potency of the peripheral cholecystokinin (CCK) satiation-signaling system mediates part of E2's influence on feeding in rats, the influence of ip injections of 250 mug of the selective CCKA receptor antagonist devazepide was then tested. Devazepide increased 3-h food intake in E2-treated WT mice, but was ineffective in both groups of alpha ERKO mice. Furthermore, ip injections of 4 mug/kg CCK-8 increased the number of cells expressing c-Fos immunoreactivity in the nuclei of the solitary tract of E2-treated WT mice more than it did in vehicle-treated WT mice, whereas E2 had no such effect in alpha ERRO mice. Thus, ER alpha is necessary for normal responsivity of food intake, body weight, adiposity, and the peripheral CCK satiation-signaling system to E2 in mice, and ER beta is not sufficient for any of these effects. This is the first demonstration that ER alpha gene expression is involved in the estrogenic control of feeding behavior and weight regulation of female mice.