Orexins, also referred to as Hypocretins, are produced by specialized neurons in the lateral hypothalamus, which project to many different regions of the brain. Orexin A (33 amino acids) and Orexin B (28 amino acids) are both produced from a single pre-pro-orexin polypeptide by a cascade of enzymatic reactions. They operate via binding to two closely related G protein-coupled receptors called Orexin receptor 1 and 2 (OxR 1 and OxR 2). OxR 1 is selective for Orexin A whereas OxR 2 binds both peptides with similar affinity.
The orexin system is conserved in mammals, and plays a central role in regulating feeding, sleep/wake cycles, arousal, energy expenditure, reward seeking, cognition, and stress responses. Defects in orexin signaling are involved in diet-induced obesity, diabetes, narcolepsy, panic anxiety disorder, depression, and addiction.