Amygdala-liver signalling orchestrates glycaemic responses to stress

Behavioural adaptations to environmental threats are crucial for survival^1,2 and necessitate rapid deployment of energy reserves^3-5. The amygdala coordinates behavioural adaptations to threats⁶, 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^VMH neurons), which precipitates hyperglycaemia and hypophagia. The glycaemic actions of MeA^VMH 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.