Hypothalamic insulin signalling as a nexus regulating mood and metabolism

Insulin has long been known as a metabolic hormone critical in the treatment of diabetes for its peripheral effects on blood glucose. However, in the last 50 years, insulin has entered the realm of neuroendocrinology and many studies have described its function on insulin receptors in the brain in relation to both metabolic and mood disorders. Indeed, rodent models of impaired insulin signalling show signs of dysregulated energy and glucose homeostasis, as well as anxiety-like and depressive behaviours. Importantly, many metabolic diseases such as obesity and diabetes increase the risk of developing mood disorders; however, the brain mechanisms underlying the connection between metabolism and mood remain unresolved. We present the current literature on the importance of the insulin receptor with respect to regulating glucose and energy homeostasis and mood-related behaviours. Specifically, we hypothesise that the insulin receptor in the hypothalamus, classically known as the homeostatic centre of the brain, plays a causal role in linking metabolic and behavioural effects of insulin signalling. In this review, we discuss insulin signalling in the hypothalamus as a critical point of neural integration controlling metabolism and mood.