Therapeutic access points: The roles of circumventricular organs in drug delivery and metabolic regulation

The current obesity drug landscape, dominated by GLP-1 receptor agonists and emerging multi-agonist therapies, has reinforced that long-term weight loss is achieved in large part through central mechanisms that suppress appetite and reshape energy balance. Consequently, there is a renewed focus on how peripherally administered agents access the brain to exert these pharmacological effects. Circumventricular organs (CVOs) constitute specialised brain-blood interfaces that detect circulating metabolic, hormonal and inflammatory signals and relay them to neural circuits regulating cardiovascular function, reproduction and energy homeostasis. We recapitulate the organisation and physiological roles of CVOs, with particular emphasis on the median eminence and area postrema. These structures represent key sites of action for anti-obesity drugs, gating the entry and signalling of GLP-1 receptor agonists, and integrating information on energy status and inflammatory challenges. We discuss how dysregulation of these interfaces may contribute to obesity pathogenesis and how targeting CVO-specific mechanisms may refine future pharmacotherapies.