Orexin/Hypocretin System: Obesity, Narcolepsy and Beyond

Obesity is an epidemic that has plagued industrialized nations for decades. However, before effective treatments can be implemented, the pathways and transmitters involved in appetite and food-seeking behavior must first be resolved. Food-seeking behavior involves the integration of three separate systems: appetite, wakefulness and an increase in sympathetic activity. The recent discovery of two hypothalamic peptides, orexin A/hypocretin 1 and orexin B/hypocretin 2, found exclusively in the lateral hypothalamus, may lead to a better understanding of how the integration of these three systems involved in appetite are modulated through a common neurotransmitter. Two known receptors, OX1R and OX2R, have been reported and are expressed throughout the entire neuraxis. The physiological role of orexin/hypocretin relative to food intake, sleep-wake cycling and autonomic activity has emerged in both animals and humans. The increased understanding of the orexin system has directed attention to the development of novel chemicals acting on orexin receptors as potential targets for obesity, narcolepsy and cardiovascular disease