Identification of a Peptidergic Pathway Critical to Satiety Responses in Drosophila

Although several neural pathways have been implicated in feeding behaviors in mammals [1–7], it remains unclear how the brain coordinates feeding motivations to maintain a constant body weight (BW). Here, we identified a neuropeptide pathway important for the satiety and BW control in Drosophila. Silencing of myoinhibitory peptide (MIP) neurons significantly increased BW through augmented food intake and fat storage. Likewise, the loss-of-function mutation of mip also increased feeding and BW. Suppressing the MIP pathway induced satiated flies to behave like starved ones, with elevated sensitivity toward food. Conversely, activating MIP neurons greatly decreased food intake and BW and markedly blunted the sensitivity of starved flies toward food. Upon terminating the activation protocol of MIP neurons, the decreased BW reverts rapidly to the normal level through a strong feeding rebound, indicating the switch-like role of MIP pathway in feeding. Surprisingly, the MIP-mediated BW decrease occurred independently of sex peptide receptor (SPR), the only known receptor for MIP, suggesting the presence of a yet-unknown MIP receptor. Together, our results reveal a novel anorexigenic pathway that controls satiety in Drosophila and provide a new avenue to study how the brain actively maintains a constant BW. [Display omitted] •Activity of myoinhibitory peptide (MIP) neurons is tightly linked to body weight•MIP encodes anorexigenic brain signaling that determines body weight•MIP produces satiety responses independently of sex peptide receptor•MIP modulates behavioral responses to olfactory and gustatory cues of food Min et al. uncover that myoinhibitory peptide and myoinhibitory peptide neurons in the brain are important for shaping feeding motivations and maintaining body weight in Drosophila. Like the pro-opiomelanocortin pathway in mammals, silencing myoinhibitory peptide neurons increases feeding activity and body weight drastically.