A Cross-Species Atlas of the Dorsal Vagal Complex Reveals Neural Mediators of Cagrilintide's Effects on Energy Balance.

ABSTRACT: Amylin analogs, including potential anti-obesity therapies like cagrilintide, act on neurons in the brainstem dorsal vagal complex (DVC) that express calcitonin receptors (CALCR). These receptors, often combined with receptor activity-modifying proteins (RAMPs), mediate the suppression of food intake and body weight. To understand the molecular and neural mechanisms of cagrilintide action, we used single-nucleus RNA sequencing to define 89 cell populations across the rat, mouse, and non-human primate caudal brainstem. We then integrated spatial profiling to reveal neuron distribution in the rat DVC. Furthermore, we compared the acute and long-term transcriptional responses to cagrilintide across DVC neurons of rats, which exhibit strong cagrilintide responsiveness, and mice, which respond

SUBMITTER: Ludwig MQ 

PROVIDER: S-EPMC11760743 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature