SUMMARYThe hormonal regulation of feeding behaviour is well known in vertebrates,whereas it remains poorly understood in insects. Here, we report that the takeout gene is an essential component of nutritional homeostasis in Drosophila. takeout encodes a putative juvenile hormone (JH)binding protein and has been described as a link between circadian rhythm and feeding behaviour. However, the physiological role of takeout and its putative link to JH remain unknown. In this study, we show that takeout (to1) flies failed to adapt their food intake according to food availability and that most defects could be genetically rescued. When food is abundant, to1 are hyperphagic, yielding to hypertrophy of the fat body. When food reappears after a starvation period, to1 flies do not increase their food intake as much as wild-type flies. This defect in food intake regulation is partly based on the action of Takeout on taste neurons, because the sensitivity of to1 gustatory neurons to sugars does not increase after starvation, as in wild-type neurons. This lack of regulation is also evident at the locomotor activity, which normally increases during starvation, a behaviour related to food foraging. In addition, to1 flies lack sexual dimorphism of locomotor activity,which has previously been linked to the JH circulating level. Moreover,application of the JH analog methoprene rescues the phenotype. These results suggest that takeout plays a central role as a feeding regulator and may act by modulating the circulating JH level.