Across many species, animals carefully regulate their food intake according to their energy needs. They are able to do so through the ability to sense hunger or satiety cues. In vertebrates, these signals are released by the gastrointestinal tract and by adipose tissue, and reach feeding centers in the brain, where they stimulate the release of peptides that modulate feeding behavior (Benarroch, 2010; Berthoud, 2008). Although many of these neuronal populations have been identified in rodent models, the neural circuitry behind behavioral modification of food intake remains largely unknown. Insects like the blowfly and the locust have classically been used to describe basic features of feeding behavior (Bernays and Chapman, 1974; Dethier, 1976). These animals, as well as vinegar flies and mosquitoes have been shown to modify their feeding behavior according to their internal nutritional status (Edgecomb et al., 1994; Takken et al., 2001). Thus they are good models for examining the question of how this modulation of behavior occurs. Moreover, Drosophila melanogaster has been used to study mechanisms of complex behaviors to great effect, and there are ample genetic tools available to study feeding behavior in this organism (Vosshall, 2007). We set out to identify genes that regulate feeding behavior according to nutritional status. Anopheles gambiae mosquitoes were previously shown to display reduced host-seeking behavior for forty-eight hours after taking a bloodmeal (Takken et al., 2001). We used whole genome microarrays to look for genes that are regulated in olfactory tissue by blood-feeding, and that therefore might function to modify olfactory driven host-seeking behavior according to nutritional state. We found that two odorant receptor genes are significantly regulated by blood-feeding. These are therefore candidate receptors for ligands that are important for host-seeking. We then extended our studies to Drosophila with the goal of identifying novel regulators of post-fasting feeding behavior. First we defined two stereotypical post-fasting behaviors in flies: increased attraction to food odor, and increased consumption of liquid food. We then looked for candidate genes that regulate these behaviors by looking for transcripts that are regulated by fasting and found that 247 genes in the head are significantly regulated by nutritional status. Finally, we carried out a targeted genetic screen using RNA interference against these candidate genes. We looked for flies that show a defective post fasting food intake response, and found eleven genes that cause such a behavioral disruption. These genes may represent novel regulators of hunger and satiety in insects, laying the groundwork for future studies of modification of feeding behavior
