Orexin Drives Energy Expenditure

Abstract Orexins are involved in a variety of behaviors, including the ability to induce spontaneous physical activity (SPA). This type of activity includes all nonexercise physical activity (e.g., what could be considered restlessness) and represents an unconscious drive for movement. The calories expended via SPA are physiologically relevant to human energy balance and are controlled by a distributed brain network that includes several neural systems. The hypothalamic orexin neurons play a key role in generating SPA and NEAT (nonexercise activity thermogenesis or NEAT) ( Kotz et al., 2008 ; Teske et al., 2008 ). These neural systems are yet to be fully described, but are attractive therapeutic targets for obesity prevention and/or treatment. In this review, we focus on evidence supporting a positive effect of orexins on energy expenditure through SPA, in the context of the potential for orexin to have a therapeutic role in obesity.