Roles of Orexins and Orexin Receptors in Central Regulation of Feeding Behavior and Energy Homeostasis

Orexins were initially recognized as regulators of feeding behavior due to their exclusively production in the lateral hypothalamic area (LHA), a feeding center. Subsequently, the finding that orexin deficiency causes narcolepsy in humans and animals suggested that these hypothalamic neuropeptides play a critical role in regulating and maintaining sleep/wakefulness states. Proper maintenance of arousal during food searching and intake is essential for an animal's survival. Therefore, feeding behavior and sleep/wakefulness states are appropriately coordinated. For example, when faced with reduced food availability, animals adapt with a longer wakefulness period, which disrupts the normal circadian pattern of activity. The discovery that orexin neurons are regulated by peripheral metabolic cues, including ghrelin, leptin and glucose, suggests that they might have important roles as a link between energy homeostasis and sleep/wakefulness states. Recent studies on afferent (input) systems of orexin neurons further suggest roles of orexin and orexin receptors in the coordination of feeding, arousal and emotion.