The ETS-5 transcription factor regulates activity states in <i>Caenorhabditis elegans</i> by controlling satiety.

Abstract

Animal behavior is shaped through interplay among genes, the environment, and previous experience. As in mammals, satiety signals induce quiescence in <i>Caenorhabditis elegans</i> Here we report that the <i>C. elegans</i> transcription factor ETS-5, an ortholog of mammalian FEV/Pet1, controls satiety-induced quiescence. Nutritional status has a major influence on <i>C. elegans</i> behavior. When foraging, food availability controls behavioral state switching between active (roaming) and sedentary (dwelling) states; however, when provided with high-quality food, <i>C. elegans</i> become sated and enter quiescence. We show that ETS-5 acts to promote roaming and inhibit quiescence by setting the internal "satiety quotient" through fat regulation. Acting from the ASG and BAG sensory neurons, we show that ETS-5 functions in a complex network with serotonergic and neuropeptide signaling pathways to control food-regulated behavioral state switching. Taken together, our results identify a neuronal mechanism for controlling intestinal fat stores and organismal behavioral states in <i>C. elegans</i>, and establish a paradigm for the elucidation of obesity-relevant mechanisms.