Woodie Lauren N, Melink Lily C, Midha Mohit, de Araújo Alan M, Geisler Caroline E, Alberto Ahren J, Krusen Brianna M, Zundell Delaine M, de Lartigue Guillaume, Hayes Matthew R, Lazar Mitchell A
bioRxiv. 2023 Dec 1:2023.11.30.568080. doi: 10.1101/2023.11.30.568080.
Circadian desynchrony induced by shiftwork or jetlag is detrimental to metabolic health, but how synchronous/desynchronous signals are transmitted among tissues is unknown. Here we report that liver molecular clock dysfunction is signaled to the brain via the hepatic vagal afferent nerve (HVAN), leading to altered food intake patterns that are corrected by ablation of the HVAN. Hepatic branch vagotomy also prevents food intake disruptions induced by high-fat diet feeding and reduces body weight gain. Our findings reveal a previously unrecognized homeostatic feedback signal that relies on synchrony between the liver and the brain to control circadian food intake patterns. This identifies the hepatic vagus nerve as a therapeutic target for obesity in the setting of chrono-disruption.
The hepatic vagal afferent nerve signals internal circadian desynchrony between the brain and liver to induce maladaptive food intake patterns.
轮班工作或时差导致的昼夜节律失调对代谢健康有害，但同步/不同步信号如何在组织间传递尚不清楚。我们在此报告，肝脏分子时钟功能障碍通过肝迷走传入神经（HVAN）向大脑发出信号，导致食物摄入模式改变，而通过切断HVAN可纠正这种改变。肝支迷走神经切断术还可防止高脂饮食引起的食物摄入紊乱，并减少体重增加。我们的研究结果揭示了一种先前未被认识的稳态反馈信号，该信号依赖于肝脏和大脑之间的同步来控制昼夜食物摄入模式。这确定了肝迷走神经是昼夜节律紊乱情况下肥胖症的治疗靶点。
肝迷走传入神经发出大脑和肝脏之间内部昼夜节律失调的信号，以诱导适应不良的食物摄入模式。
