Hypocretins/Orexins

This Research Topic of Frontiers in Endocrinology is aimed to celebrate the 20th anniversary of the discovery of hypocretin/orexin. The discovery of this neuropeptide was important because it provided the identification of a subset of neurons located in the lateral hypothalamus; a region known to express other neuropeptides such as MCH, CART or neurotensin. This was a very exciting finding for two main reasons. Firstly, the lateral hypothalamus was known to play a key role in the control of neuroendocrine function, energy and metabolic homeostasis as well as reward and emotion. Moreover, despite the very precise and unique localization of their bodies, these hypocretin/orexin neurons were found to project widely in the brain, to areas such as the VTA, amygdala and the locus coeruleus.

Data gleaned since then fulfill many of the initial expectations regarding the biological relevance of the hypocretin/orexin system. One of the key findings was its characterization as one of the key mechanisms on sleep/wake regulation. This led to further developments including the use of measurements of hypocretin/orexin in CSF as a diagnostic biomarker in narcolepsy and the therapeutic use of agonists/antagonists in the treatment of narcolepsy or insomnia. Considering the presence of this neuropeptide in the hypothalamus and its involvement in the sleep/wake cycle it is unsurprising its involvement in the control of pituitary hormone secretion as well as in energy and metabolic homeostasis.

In this issue, we welcome contributions that will untangle the hypocretin/orexin system from its early identification to uncover its biological effects. We aim to provide readers with a clear view on the physiological relevance, diagnostic potential and therapeutic implications of the hypocretin/orexin system.