Orexin: a link between energy homeostasis and adaptive behaviour.

Orexins, also called hypocretins, are a pair of neuropeptides expressed by a specific population of neurons in the lateral hypothalamic area, a region of the brain implicated in feeding, arousal and motivated behaviour. The purpose of this review is to summarize recent relevant findings on orexins, and discuss the physiological roles of these peptides.Recent findings suggest that orexin neurons provide a critical link between the peripheral energy balance and central nervous system mechanisms that coordinate sleep-wakefulness and motivated behaviours such as food seeking, especially in the physiological state of fasting stress.Orexin (hypocretin) neurons interact with feeding centres in the hypothalamus, arousal and sleep-wakefulness centres in the brainstem, sympathetic and parasympathetic nuclei and the limbic system. The central administration of orexin dose-dependently increases food intake, waking time, motor activity, and metabolic rate, as well as heart rate and blood pressure in many species. Recent electrophysiological studies have shown that orexin neurons are regulated by metabolic cues, including leptin, glucose, and ghrelin, as well as monoamines and acetylcholin. Orexin neurons thus have the requisite functional interactions with hypothalamic feeding pathways and monoaminergic-cholinergic centres in the brain stem, and regulation by nutritional factors, to suggest that they may be an important cellular link in the integration of adaptive behaviour associated with arousal and energy homeostasis.