Hepatic Vagal Afferents Convey Clock-Dependent Signals to Regulate Circadian Food Intake Patterns

Circadian desynchrony induced by shiftwork or jetlag 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 chrono-disruption. Overall design: Arcuate nucleus microdissections and left nodose ganglia from control and HepDKO animals were collected every 6hrs for 24hrs and sequenced. 3-4 arcuate nuclei per group per time point were pooled for each biological replicate. 4 left nodose per group per time point were pooled for each biological replicate.