Objective

Estrogen protects animals from obesity through estrogen receptor α (ERα), partially by inhibiting overeating in animals fed ad libitum. However, the effects of estrogen on feeding behavior in hungry animals remain unclear. In this study, we examined the roles of 17β-estradiol (E2) and ERα in the regulation of feeding in hungry female animals and explored the underlying mechanisms.

Methods

Wild-type female mice with surgical depletion of endogenous estrogens were used to examine the effects of E2 supplementation on acute refeeding behavior after starvation. ERα-C451A mutant mice deficient in membrane-bound ERα activity and ERα-AF2⁰ mutant mice lacking ERα transcriptional activity were used to further examine mechanisms underlying acute feeding triggered by either fasting or central glucopenia (induced by intracerebroventricular injections of 2-deoxy-D-glucose). We also used electrophysiology to explore the impact of these ERα mutations on the neural activities of ERα neurons in the hypothalamus.

Results

In the wild-type female mice, ovariectomy reduced fasting-induced refeeding, which was restored by E2 supplementation. The ERα-C451A mutation, but not the ERα-AF2⁰ mutation, attenuated acute feeding induced by either fasting or central glucopenia. The ERα-C451A mutation consistently impaired the neural responses of hypothalamic ERα neurons to hypoglycemia.

Conclusion

In addition to previous evidence that estrogen reduces deviations in energy balance by inhibiting eating at a satiated state, our findings demonstrate the unexpected role of E2 that promotes eating in hungry mice, also contributing to the stability of energy homeostasis. This latter effect specifically requires membrane-bound ERα activity.

中文翻译：

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17β-雌二醇通过膜启动的 ERα 信号促进饥饿小鼠的急性再进食。

客观的

雌激素通过雌激素受体 α (ERα) 保护动物免于肥胖，部分是通过抑制随意喂食的动物暴饮暴食。然而，雌激素对饥饿动物摄食行为的影响仍不清楚。在这项研究中，我们研究了 17β-雌二醇 (E2) 和 ERα 在调节饥饿雌性动物摄食中的作用，并探讨了其潜在机制。

方法

使用手术消耗内源性雌激素的野生型雌性小鼠来检查补充 E2 对饥饿后急性再进食行为的影响。缺乏膜结合 ERα 活性的 ERα-C451A 突变小鼠和缺乏 ERα 转录活性的ERα-AF2 ⁰突变小鼠被用于进一步检查由禁食或中枢性葡萄糖减少（由脑室内注射 2-脱氧-D诱导）引发的急性进食的潜在机制-葡萄糖）。我们还使用电生理学来探索这些 ERα 突变对下丘脑 ERα 神经元神经活动的影响。

结果

在野生型雌性小鼠中，卵巢切除术减少了禁食诱导的再进食，而 E2 补充剂可以恢复这种情况。ERα-C451A 突变，但不是 ERα-AF2 ⁰突变，减弱了由空腹或中枢性葡萄糖减少引起的急性进食。ERα-C451A 突变始终损害下丘脑 ERα 神经元对低血糖的神经反应。

结论

除了先前的证据表明雌激素通过抑制饱食状态下的进食来减少能量平衡的偏差之外，我们的研究结果还证明了 E2 在促进饥饿小鼠进食方面的意外作用，也有助于能量稳态的稳定性。后一种效应特别需要膜结合的 ERα 活性。