Department of Biology, University of Virginia, Charlottesville, United States.
Department of Biological Chemistry and Pharmacology, The Ohio State University College of Medicine, Columbus, United States.
Elife. 2020 Jan 29;9:e52623. doi: 10.7554/eLife.52623.
Networks of neurons control feeding and activity patterns by integrating internal metabolic signals of energy balance with external environmental cues such as time-of-day. Proper circadian alignment of feeding behavior is necessary to prevent metabolic disease, and thus it is imperative that molecular players that maintain neuronal coordination of energy homeostasis are identified. Here, we demonstrate that mice lacking the p75 neurotrophin receptor, p75NTR, decrease their feeding and food anticipatory behavior (FAA) in response to daytime, but not nighttime, restricted feeding. These effects lead to increased weight loss, but do not require p75NTR during development. Instead, p75NTR is required for fasting-induced activation of neurons within the arcuate hypothalamus. Indeed, p75NTR specifically in AgRP neurons is required for FAA in response to daytime restricted feeding. These findings establish p75NTR as a novel regulator gating behavioral response to food scarcity and time-of-day dependence of circadian food anticipation.
神经元网络通过将内部代谢信号与外部环境线索（如一天中的时间）相整合来控制进食和活动模式。适当的进食行为与昼夜节律同步对于预防代谢疾病是必要的，因此，必须确定维持神经元能量稳态协调的分子参与者。在这里，我们证明缺乏 p75 神经生长因子受体（p75NTR）的小鼠会减少白天而非夜间限时进食时的摄食和摄食前行为（FAA）。这些影响导致体重增加，但在发育过程中不需要 p75NTR。相反，p75NTR 是在限时进食期间弓状下丘脑神经元激活所必需的。事实上，p75NTR 特异性在 AgRP 神经元中是对白天限时进食时 FAA 的响应所必需的。这些发现确立了 p75NTR 作为一种新型调节剂，可调节对食物匮乏的行为反应以及昼夜节律性食物预期的时间依赖性。
