The current obesity epidemic mainly results from high‐fat high‐caloric diet (HFD ) feeding and may also be contributed by chronic stress; however, the neural basis underlying stress‐related diet‐induced obesity remains unknown. Corticotropin‐releasing hormone (CRH ) neurons in the paraventricular hypothalamus (PVH ), a known body weight‐regulating region, represent one key group of stress‐responsive neurons. Here, we found that HFD feeding blunted PVH CRH neuron response to nutritional challenges as well as stress stimuli and dexamethesone, which normally produce rapid activation and inhibition on these neurons, respectively. We generated mouse models with the activity of these neurons clamped at high or low levels, both of which showed HFD ‐mimicking, blunted PVH CRH neuron responsiveness. Strikingly, both models developed rapid HFD ‐induced obesity, associated with HFD ‐mimicking, reduced diurnal rhythmicity in feeding and energy expenditure. Thus, blunted responsiveness of PVH CRH neurons, but not their absolute activity levels, underlies HFD ‐induced obesity and may also contribute to stress‐induced obesity.

中文翻译：

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下丘脑CRH神经元反应中断会导致饮食诱发的肥胖。

当前的肥胖病流行主要是由于高脂高热量饮食（HFD）喂养造成的，也可能是由慢性压力引起的；然而，与压力有关的饮食引起的肥胖的神经基础仍然是未知的。下丘脑下丘脑（PVH）中的促肾上腺皮质激素释放激素（CRH）神经元是一个已知的体重调节区域，是应激反应神经元的关键组成部分。在这里，我们发现HFD喂养使PVH CRH神经元对营养挑战以及应激刺激和地塞米松的反应减弱，后者通常分别对这些神经元产生快速激活和抑制作用。我们生成的小鼠模型将这些神经元的活性钳制在高或低水平，二者均显示出类似于HFD的模仿，钝化的PVH CRH神经元反应性。惊人地 两种模型均产生了由HFD引起的快速肥胖症，并伴有HFD模仿，降低了喂养和能量消耗的昼夜节律。因此，PVH CRH神经元反应迟钝，而不是其绝对活性水平，是HFD诱发肥胖的基础，也可能有助于应激诱发肥胖。