Hypothalamic regulation of sepsis-associated anorexia: cytokine and hormonal signalling through AgRP/POMC circuits

Sepsis is a life-threatening syndrome resulting from a dysregulated host response to an infection and is considered as a major global health priority. Despite increased metabolic energy needs to fight the infection and to sustain the inflammatory response, anorexia is one of the main characteristics of sickness behaviour during sepsis. In this review, we address the question of how feeding behaviour is regulated under basal conditions at the level of the hypothalamus, with specific focus on the orexigenic agouti-related peptide (AgRP)/neuropeptide Y (NPY)-expressing neurons and the anorexigenic pro-opiomelanocortin (POMC)/cocaine and amphetamine-regulated transcript (CART)-expressing neurons present in the arcuate nucleus. This is mediated by neural and humoral pathways involving the vagal nerve, and the blood-brain barrier and circumventricular organs, respectively. Furthermore, we discuss recent advances in how sepsis affects these appetite-controlling mechanisms by impairing the central integration of these peripheral signals and suggest potential therapeutic targets that might prevent or revert sepsis-associated anorexia.