Identification of a Peptidergic Pathway Critical to Satiety Responses in Drosophila

Abstract

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.

Neuropeptide relay between SIFa signaling controls the experience-dependent mating duration of male Drosophila

“…The nodes of those neural circuits activated either by appetite or satiety signals presumably inhibit each other at some level to facilitate sharply delineated behavioural outcomes. It has been known that neuropeptides and hormones are important neural substrates for modulating appetite and satiety control [6,29]. SIFa has been known as a central modulator in parallel inhibition between orexigenic and anorexigenic pathways.…”

A fat-derived metabolite regulates a peptidergic feeding circuit in Drosophila

“…The following flies are described elsewhere: S 1 106-GAL4 [13], FB-GAL4 [18], TH-GAL4 [31], Trh-GAL4 [32], c673a-GAL4 [24], Dilp2-GAL4 [33], sNPF-GAL4 [34], AstA-GAL4 [35], and UAS-Shibire ts [36]. …”

A Leptin Analog Locally Produced in the Brain Acts via a Conserved Neural Circuit to Modulate Obesity-Linked Behaviors in Drosophila

“…While neural circuits contributing to these complex behaviors in mammals continue to be the subject of intense research (Sohn et al, 2013), in recent years Drosophila has emerged as an expedient model to study central nervous system control of food intake and body weight (Al-Anzi et al, 2010; Albin et al, 2015; Dus et al, 2015; Mann et al, 2013; Min et al, 2016; Miyamoto et al, 2012; Schoofs et al, 2014). Drosophila Neuropeptide F’s (npf) role regulating food odor valuation (Beshel and Zhong, 2013) and promoting food intake (Hergarden et al, 2012; Wu et al, 2003) is particularly intriguing given its homology to mammalian Neuropeptide Y (NPY) (Brown et al, 1999), a prominent regulator of food-related appetitive behavior (Day et al, 2005; Flood and Morley, 1991).…”