CCAP regulates feeding behavior via the NPF pathway inDrosophilaadults

Abstract

The intake of macronutrients is crucial for the fitness of any animal and is mainly regulated by peripheral signals to the brain. How the brain receives and translates these peripheral signals or how these interactions lead to changes in feeding behavior is not well-understood. We discovered that 2 crustacean cardioactive peptide (CCAP)-expressing neurons in Drosophila adults regulate feeding behavior and metabolism. Notably, loss of CCAP, or knocking down the CCAP receptor (CCAP-R) in 2 dorsal median neurons, inhibits the release of neuropeptide F (NPF), which regulates feeding behavior. Furthermore, under starvation conditions, flies normally have an increased sensitivity to sugar; however, loss of CCAP, or CCAP-R in 2 dorsal median NPF neurons, inhibited sugar sensitivity in satiated and starved flies. Separate from its regulation of NPF signaling, the CCAP peptide also regulates triglyceride levels. Additionally, genetic and optogenetic studies demonstrate that CCAP signaling is necessary and sufficient to stimulate a reflexive feeding behavior, the proboscis extension reflex (PER), elicited when external food cues are interpreted as palatable. Dopaminergic signaling was also sufficient to induce a PER. On the other hand, although necessary, NPF neurons were not able to induce a PER. These data illustrate that the CCAP peptide is a central regulator of feeding behavior and metabolism in adult flies, and that NPF neurons have an important regulatory role within this system.

Bilberry (Vaccinium myrtillus L.) Extracts Comparative Analysis Regarding Their Phytonutrient Profiles, Antioxidant Capacity along with the In Vivo Rescue Effects Tested on a Drosophila melanogaster High-Sugar Diet Model

“…Starting 24 h from eclosion, only 2 residual neurons in Drosophila express CCAP (crustacean cardioactive peptide), a gene extensively studied in the context of ecdysis [272,273], recently proved to signal for food intake and regulate the triglyceride metabolism. The adult flies lacking the CCAP peptide had significantly lower triglyceride levels [274]. This correlates with the expression levels observed by us upon supplementation of the high-sugar diet with hydro-methanolic bilberry extract (E3).…”

Hormonal axes in Drosophila: regulation of hormone release and multiplicity of actions

“…AstA regulates IPCs, inhibits feeding and promotes sleep (Chen et al 2016b ; Hentze et al 2015 ; Hergarden et al 2012 ; Wang et al 2012a ). The two CCAP neurons regulate a set of two NPF neurons (NPFa) and thus modulate sugar preference and stimulate feeding (Williams et al 2020 ). In larvae, Hugin neurons receive inputs from gustatory neurons and inhibit feeding (Melcher and Pankratz 2005 ); in adults, these neurons relay hunger signals to SIFa neurons and thereby affect appetite and feeding (Martelli et al 2017 ).…”

“…LHLK neurons use LK to regulate IPCs but also other neuronal circuits to regulate metabolism and sleep, as well as water- and sugar-associated memory formation (Senapati et al 2019 ; Yurgel et al 2019 ; Zandawala et al 2018b ). NPF neurons have been extensively studied in stimulation of larval feeding (Shen and Cai 2001 ; Wang et al 2013 ; Wu et al 2005 ) but these neurons are also important in adult feeding (Chung et al 2017 ; Pu et al 2018 ; Tsao et al 2018 ; Williams et al 2020 ). SIFa neurons are central in balancing feeding, sleep and reproductive behavior (Dreyer et al 2019 ; Martelli et al 2017 ; Terhzaz et al 2007 ) and will be dealt with in more detail below.…”

Leucokinin and Associated Neuropeptides Regulate Multiple Aspects of Physiology and Behavior in Drosophila

“…The peptides are AstA, allatostatin A; DSK, drosulfakinin; ITP, ion transport peptide; TK, tachykinin: sNPF, short neuropeptide F; SIFa, SIFamide; CRZ, corazonin; Hugin, hugin-pyrokinin; NPF, neuropeptide F; CCAP, crustacean cardioactive peptide. Data used for compilation of this figure are from [1,7,141,[173][174][175][176]. B.…”