Central leptin signalling: beyond the arcuate nucleus

Leptin is an adipocyte-derived hormone that plays a crucial role in the maintenance of energy balance. Work over the past 15 years has led to a detailed understanding of its signalling and sites of action, particularly its activation of the central melanocortin signalling pathway through the arcuate nucleus of the hypothalamus (ARC). However, leptin receptors are widely expressed throughout the central nervous system (CNS), with leptin acting at distinct sites and through different mechanisms to mediate energy homeostasis and feeding behaviour. Thus, although the evidence implicating the ARC as a first-order mediator of leptin's actions is both compelling and substantial, it by no means represents the totality of leptin's effects on energy homeostasis. This review focuses on recent evidence supporting central leptin signalling beyond the ARC.