Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Science. 2024 Nov 8;386(6722):673-677. doi: 10.1126/science.adn2786. Epub 2024 Nov 7.
Circadian desynchrony induced by shiftwork or jet lag is detrimental to metabolic health, but how synchronous or desynchronous signals are transmitted among tissues is unknown. We report that liver molecular clock dysfunction is signaled to the brain through 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 homeostatic feedback signal that relies on communication between the liver and the brain to control circadian food intake patterns. This identifies the hepatic vagus nerve as a potential therapeutic target for obesity in the setting of chronodisruption.
昼夜节律紊乱由轮班工作或时差引起,对代谢健康有害,但组织之间的同步或不同步信号如何传递尚不清楚。我们报告称,肝脏分子钟功能障碍通过肝迷走传入神经(HVAN)向大脑发出信号,导致食物摄入模式发生改变,而 HVAN 的消融可纠正这些改变。肝分支迷走神经切断术也可防止高脂肪饮食喂养引起的摄食紊乱,并减少体重增加。我们的发现揭示了一种依赖于肝脏和大脑之间通讯的稳态反馈信号,以控制昼夜节律性摄食模式。这表明肝迷走神经可能成为chronodisruption 背景下肥胖的潜在治疗靶点。