AUTHOR=Chieffi Sergio , Carotenuto Marco , Monda Vincenzo , Valenzano Anna , Villano Ines , Precenzano Francesco , Tafuri Domenico , Salerno Monica , Filippi Nicola , Nuccio Francesco , Ruberto Maria , De Luca Vincenzo , Cipolloni Luigi , Cibelli Giuseppe , Mollica Maria P. , Iacono Diego , Nigro Ersilia , Monda Marcellino , Messina Giovanni , Messina Antonietta TITLE=Orexin System: The Key for a Healthy Life JOURNAL=Frontiers in Physiology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2017.00357 DOI=10.3389/fphys.2017.00357 ISSN=1664-042X ABSTRACT=

The orexin-A/hypocretin-1 and orexin-B/hypocretin-2 are neuropeptides synthesized by a cluster of neurons in the lateral hypothalamus and perifornical area. Orexin neurons receive a variety of signals related to environmental, physiological and emotional stimuli, and project broadly to the entire CNS. Orexin neurons are “multi-tasking” neurons regulating a set of vital body functions, including sleep/wake states, feeding behavior, energy homeostasis, reward systems, cognition and mood. Furthermore, a dysfunction of orexinergic system may underlie different pathological conditions. A selective loss orexin neurons was found in narcolepsia, supporting the crucial role of orexins in maintaining wakefulness. In animal models, orexin deficiency lead to obesity even if the consume of calories is lower than wildtype counterpart. Reduced physical activity appears the main cause of weight gain in these models resulting in energy imbalance. Orexin signaling promotes obesity resistance via enhanced spontaneous physical activity and energy expenditure regulation and the deficiency/dysfunction in orexins system lead to obesity in animal models despite of lower calories intake than wildtype associated with reduced physical activity. Interestingly, orexinergic neurons show connections to regions involved in cognition and mood regulation, including hippocampus. Orexins enhance hippocampal neurogenesis and improve spatial learning and memory abilities, and mood. Conversely, orexin deficiency results in learning and memory deficits, and depression.