High-calorie diets uncouple hypothalamic oxytocin neurons from a gut-to-brain satiation pathway via κ-opioid signaling

Oxytocin-expressing paraventricular hypothalamic neurons (PVN^(OT) neurons) integrate afferent signals from the gut, including cholecystokinin (CCK), to adjust whole-body energy homeostasis. However, the molecular underpinnings by which PVN^(OT) neurons orchestrate gut-to-brain feeding control remain unclear. Here, we show that mice undergoing selective ablation of PVN^(OT) neurons fail to reduce food intake in response to CCK and develop hyperphagic obesity on a chow diet. Notably, …