Mating activates neuroendocrine pathways signaling hunger in Drosophila females.

Mated females reallocate resources to offspring production, causing changes to nutritional requirements and challenges to energy homeostasis. Although observed across species, the neural and endocrine mechanisms that regulate the nutritional needs of mated females are not well understood. Here, we find that mated Drosophila melanogaster females increase sugar intake, which is regulated by the activity of sexually dimorphic insulin receptor (Lgr3) neurons. In virgins, Lgr3+ cells have reduced activity as they receive inhibitory input from active, female-specific pCd-2 cells, restricting sugar intake. During copulation, males deposit sex peptide into the female reproductive tract, which silences a three-tier mating status circuit and initiates the female postmating response. We show that pCd-2 neurons also become silenced after mating due to the direct synaptic input from the mating status circuit. Thus, in mated females pCd-2 inhibition is attenuated, activating downstream Lgr3+ neurons and promoting sugar intake. Together, this circuit transforms the mated signal into a long-term hunger signal. Our results demonstrate that the mating circuit alters nutrient sensing centers to increase feeding in mated females, providing a mechanism to increase intake in anticipation of the energetic costs associated with reproduction.