美国哈佛医学院Bradford B. Lowell等研究人员，合作揭示了刺鼠相关肽饥饿神经元的急性和昼夜前馈调节。相关论文于2024年12月23日在线发表在《细胞—代谢》杂志上。

研究人员表示，当食物自由供应时，进食发生时并未出现能量赤字。尽管刺鼠相关肽（AgRP）神经元可能参与其中，但它们的激活通常认为需要负能量平衡。

为研究这一点，研究人员在小鼠体内实施了长期连续的光纤光度计记录。研究人员发现了AgRP神经元调控的新形式，包括在进食前快速的活动下降，以及由于禁食引起的意外快速激活。此外，AgRP神经元活动呈现昼夜节律，且其活动在每日进食开始时达到高峰。

重要的是，当营养通过恒速胃肠输注提供时，这一节律仍然存在。因此，它并非是次于昼夜进食节律的结果。AgRP神经元的节律由昼夜生物钟驱动，视交叉上核（SCN）通过从背内侧下丘脑（DMH^Trh神经元），释放促甲状腺激素的神经元的兴奋性传入，激活AgRP神经元，从而驱动每日进食节律。

附：英文原文

Title: Acute and circadian feedforward regulation of agouti-related peptide hunger neurons

Author: Amelia M. Douglass, Hakan Kucukdereli, Joseph C. Madara, Daqing Wang, Chen Wu, Elijah D. Lowenstein, Jenkang Tao, Bradford B. Lowell

Issue&Volume: 2024-12-23

Abstract: When food is freely available, eating occurs without energy deficit. While agouti-related peptide (AgRP) neurons are likely involved, their activation is thought to require negative energy balance. To investigate this, we implemented long-term, continuous in vivo fiber-photometry recordings in mice. We discovered new forms of AgRP neuron regulation, including fast pre-ingestive decreases in activity and unexpectedly rapid activation by fasting. Furthermore, AgRP neuron activity has a circadian rhythm that peaks concurrent with the daily feeding onset. Importantly, this rhythm persists when nutrition is provided via constant-rate gastric infusions. Hence, it is not secondary to a circadian feeding rhythm. The AgRP neuron rhythm is driven by the circadian clock, the suprachiasmatic nucleus (SCN), as SCN ablation abolishes the circadian rhythm in AgRP neuron activity and feeding. The SCN activates AgRP neurons via excitatory afferents from thyrotrophin-releasing hormone-expressing neurons in the dorsomedial hypothalamus (DMHTrh neurons) to drive daily feeding rhythms.

DOI: 10.1016/j.cmet.2024.11.009

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00455-8