Meal timing entrains circadian rhythms in the dorsal vagal complex, a brainstem satiety centre

by Lukasz Chrobok, Charlotte Muir, Tanya Chonkria Kaur, Emily Birt, Iliana Veneri, Jingyi Kathy Li, Timna Hitrec, Michael Ambler, Anthony Edward Pickering, Hugh David Piggins

The dorsal vagal complex (DVC) includes a multi-component brainstem satiety centre which has gained attention as a key target of anti-obesity pharmacotherapies. Our recent studies revealed its circadian timekeeping properties, with molecular and electrophysiological 24 h rhythms persisting independently of the primary hypothalamic clock. However, the factors entraining these brainstem oscillators and the downstream transcriptional targets of the DVC molecular clock remain unclear. Here, using PERIOD2::LUCIFERASE reporter mice and fluorescent in situ hybridisation, we quantitatively demonstrate rhythms in core clock gene expression in the caudal DVC ex vivo and in vivo. We show that the molecular clock is associated with rhythmic expression of numerous neurotransmitter receptor genes in the DVC in vivo, with the phase of both clock and clock-controlled gene expression tightly regulated by meal timing. These findings uncover food-entrained circadian rhythms in the DVC and have important implications for clinical studies targeting brainstem satiety mechanisms.