Regulation of starvation-induced hyperactivity by insulin and glucagon signaling in adult Drosophila.

Yue Yu,Liming Wang,Junling Jia,Guo Cheng,Jie Ye,Vivian Zhang,Rui Huang,Chao Wu

doi:10.7554/elife.15693

Yue Yu, Liming Wang + Show 6 more

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https://doi.org/10.7554/elife.15693

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Abstract

Starvation induces sustained increase in locomotion, which facilitates food localization and acquisition and hence composes an important aspect of food-seeking behavior. We investigated how nutritional states modulated starvation-induced hyperactivity in adult Drosophila. The receptor of the adipokinetic hormone (AKHR), the insect analog of glucagon, was required for starvation-induced hyperactivity. AKHR was expressed in a small group of octopaminergic neurons in the brain. Silencing AKHR+ neurons and blocking octopamine signaling in these neurons eliminated starvation-induced hyperactivity, whereas activation of these neurons accelerated the onset of hyperactivity upon starvation. Neither AKHR nor AKHR+ neurons were involved in increased food consumption upon starvation, suggesting that starvation-induced hyperactivity and food consumption are independently regulated. Single cell analysis of AKHR+ neurons identified the co-expression of Drosophila insulin-like receptor (dInR), which imposed suppressive effect on starvation-induced hyperactivity. Therefore, insulin and glucagon signaling exert opposite effects on starvation-induced hyperactivity via a common neural target in Drosophila.

Highlights

Energy homeostasis is vital for survival, growth, and reproduction of animal species (Gautron et al, 2015)
Through a neuronal-specific RNAi screen, we find that a small group of octopaminergic neurons located in the subesophageal zone (SEZ) of the fly brain are both necessary and sufficient for starvation-induced hyperactivity
We crossed UAS-RNAi lines targeting 31 candidate neuropeptide receptors to a pan-neuronal GAL4 driver, elav-GAL4, and assayed their female progeny for baseline locomotion under fed conditions (Figure 1c). 16 out of the 31 lines exhibited significantly altered activity compared to the control, suggesting that the baseline locomotion may be a behavioral trait sensitive to multiple neuropeptidergic signaling systems (Supplementary file 1)

Summary

Introduction

Energy homeostasis is vital for survival, growth, and reproduction of animal species (Gautron et al, 2015). Energy deprivation drives a complex behavioral program to ensure adequate food intake (Sternson et al, 2013). The hypothalamic arcuate nucleus, especially the neurons expressing agouti-related protein (AgRP)/neuropeptide Y (NPY), and those expressing pro-opiomelanocortin (POMC), sense and integrate numerous nutritional cues such as circulating glucose, insulin, leptin, and ghrelin and modulate food intake in response (Belgardt et al, 2009). Several hormonal signals modulate different aspects of food intake, these including Drosophila insulin-like peptides (DILPs), the two homologs of mammalian NPY, neuropeptide F (NPF) and short neuropeptide F (sNPF), and a handful of other neuropeptides such as allatostatin A (AstA), leucokinin, and hugin (Pool and Scott, 2014). It is generally accepted that these hormonal cues represent the nutritional status of animals and translate them into physiological and behavioral responses (Pool and Scott, 2014; Sternson et al, 2013)

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