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.
Highlights
The intake of macronutrients is crucial for the fitness of any animal and is mainly regulated by peripheral signals to the brain
To examine the expression pattern, R64F05-GAL4 flies were crossed with UASGFP and the brains of 5- to 9-d-old F1 generation adult males were costained for green fluorescent protein (GFP) (Fig. 1B, green) and neuropeptide F (NPF) expression (Fig. 1C, magenta)
We demonstrate that 2 residual crustacean cardioactive peptide (CCAP) neurons signal for food intake and have a role in regulating metabolism, where they are important for maintaining triglyceride levels
Summary
The intake of macronutrients is crucial for the fitness of any animal and is mainly regulated by peripheral signals to the brain. We discovered that 2 crustacean cardioactive peptide (CCAP)-expressing neurons in Drosophila adults regulate feeding behavior and metabolism. 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. 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. | | | feeding behavior metabolism hypothalamus dopamine during nutrient starvation, neuropeptide F (NPF) regulates a dopaminergic to Gr5a pathway to increase sugar sensitivity in Drosophila adults, while short neuropeptide F (sNPF) signals to Gr66-expressing GRNs to reduce the inhibition to bitter taste as starvation progresses [15]. How physiological conditions affect macronutrient intake and interact with the neuronal pathways that determine macronutrient consumption are not well-understood
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