Hypocretin/orexin and energy expenditure

The hypocretins or orexins are endogenous neuropeptides synthesized in discrete lateral, perifornical and dorsal hypothalamic neurones. These multi-functional neuropeptides modulate energy homeostasis, arousal, stress, reward, reproduction and cardiovascular function. This review summarizes the role of hypocretins in modulating non-sleep-related energy expenditure with specific focus on the augmentation of whole body energy expenditure as well as hypocretin-induced physical activity and sympathetic outflow. We compare the efficacy of hypocretin-1 and 2 on energy expenditure and evaluate whether the literature implicates hypocretin signalling though the hypocretin-1 and -2 receptor as having shared and or functionally specific physiological effects. Thus far data suggest that hypocretin-1 has a more robust stimulatory effect relative to hypocretin-2. Furthermore, hypocretin-1 receptor predominantly mediates behaviours known to influence energy expenditure. Further studies on the hypocretin-2 receptor are needed.