Food for thought: understanding the multifaceted nature of orexins

Orexins are a pair of hypothalamic neuropeptides that were discovered in the late 1990s and named initially for their ability to promote feeding. Subsequent studies have revealed the importance of orexins to a variety of physiological functions, including brown fat thermogenesis, sleep/wake cycles, physical activity, and cognition. We aim to elucidate the various roles of orexins and discuss how these multiple functions are interlinked. We explain that although the unique dual roles of orexins in increasing feeding while concomitantly elevating energy expenditure appear counterproductive, they are necessary for physiological scenarios during which simultaneous stimulation of energy expenditure and feeding occur, namely diet-induced thermogenesis and arousal from hibernation. The position of orexins at the interface between sleep/wake cycles, energy homeostasis, and environmental factors has important implications in the treatment of obesity.