Amygdala-liver signalling orchestrates glycaemic responses to stress.

Behavioural adaptations to environmental threats are crucial for survival and necessitate rapid deployment of energy reserves. The amygdala coordinates behavioural adaptations to threats, but little is known about its involvement in underpinning metabolic adaptations. Here we show that acute stress activates medial amygdala (MeA) neurons that innervate the ventromedial hypothalamus (MeA neurons), which precipitates hyperglycaemia and hypophagia. The glycaemic actions of MeA neurons occur independently of adrenal or pancreatic glucoregulatory hormones. Using whole-body virus tracing, we identify a polysynaptic connection from MeA to the liver that promotes the rapid synthesis of glucose by hepatic gluconeogenesis. Repeated stress exposure disrupts MeA control of blood glucose, resulting in diabetes-like dysregulation of glucose homeostasis. Our findings reveal an amygdala-liver axis that regulates rapid glycaemic adaptations to stress and links recurrent stress to metabolic dysfunction.