Leptin receptor neurons in the dorsomedial hypothalamus regulate diurnal patterns of feeding, locomotion, and metabolism.
Leptin receptor neurons in the dorsomedial hypothalamus regulate diurnal patterns of feeding, locomotion, and metabolism.
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DOI：
10.7554/elife.63671
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发表时间：
2021-02-02
期刊：
影响因子：
7.7
通讯作者：
Morton GJ
中科院分区：
文献类型：
--
作者：
Faber CL;Deem JD;Phan BA;Doan TP;Ogimoto K;Mirzadeh Z;Schwartz MW;Morton GJ
大脑在驱动日常行为节奏和新陈代谢与环境光暗周期的和谐方面起着至关重要的作用。在大脑中，下丘脑背内侧核（DMH）参与了摄食和能量稳态的综合昼夜节律控制，但其基础细胞类型尚不清楚。在这里，我们确定了DMH瘦素受体表达（DMHLepR）神经元在这一综合控制的作用。使用病毒的方法，我们表明，沉默成年小鼠DMHLepR神经元的神经传递不仅增加体重和肥胖，但也阶段推进昼夜节律的喂养和代谢进入光周期，并取消了正常的增加，在黑暗周期的运动活动特征的夜间啮齿动物。最后，DMHLepR沉默的小鼠不能诱导食物可用性的限制性变化。总之，这些发现将DMHLepR神经元确定为每日进食时间和相关代谢节律的关键决定因素。
The brain plays an essential role in driving daily rhythms of behavior and metabolism in harmony with environmental light–dark cycles. Within the brain, the dorsomedial hypothalamic nucleus (DMH) has been implicated in the integrative circadian control of feeding and energy homeostasis, but the underlying cell types are unknown. Here, we identify a role for DMH leptin receptor-expressing (DMHLepR) neurons in this integrative control. Using a viral approach, we show that silencing neurotransmission in DMHLepR neurons in adult mice not only increases body weight and adiposity but also phase-advances diurnal rhythms of feeding and metabolism into the light cycle and abolishes the normal increase in dark-cycle locomotor activity characteristic of nocturnal rodents. Finally, DMHLepR-silenced mice fail to entrain to a restrictive change in food availability. Together, these findings identify DMHLepR neurons as critical determinants of the daily time of feeding and associated metabolic rhythms.