Original paper

The glucose–CCHamide2 pathway: a neuroendocrine mechanism linking feeding and metabolic regulation in insects

Cui, Zhebo; Zhang, Wenjing; Gao, Ziyi; Purba, Endang R.; Li, Yanbin; Sun, Jianghua; Mang, Dingze

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Entomologia Generalis Volume 46 Number 2 (2026), p. 433 - 443

published: Apr 29, 2026
published online: Mar 31, 2026
manuscript accepted: Dec 12, 2025
final revised version received: Sep 18, 2025
manuscript revision requested: Jun 20, 2025
manuscript received: Jun 7, 2025

DOI: 10.1127/entomologia/3734

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ArtNo. ESP146004602010, Price: 29.00 €

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Abstract

Energy homeostasis is crucial for insects due to high metabolic demands during growth, molting, and reproduction. The fall webworm, Hyphantria cunea, a highly polyphagous and invasive pest, exhibits remarkable physiological plasticity, including adaptive glucose homeostasis that supports survival across diverse diets and environments. However, the molecular mechanisms underlying energy regulation in H. cunea remain unclear. Here, we show that dietary glucose activates the neuropeptide CCHamide2 (CCHa2) to regulate larval metabolism. Gene expression analysis, receptor assays, and metabolic profiling revealed that glucose upregulates CCHa2 via the gustatory receptor HcGr24. Functional studies using RNA interference and CCHa2 peptide injection demonstrated that CCHa2 and its receptor, CCHa2-R, modulate the expression of insulin-like peptides (ILP2, ILP5, ILP7) in the fat body. Moreover, CCHa2/CCHa2-R signaling influences energy storage by regulating triacylglycerol and glycogen metabolism. Our results identify a previously uncharacterized glucose-Gr-CCHa2 signaling axis linking nutrient sensing to internal metabolic control in H. cunea. This work provides new insights into the neuroendocrine mechanisms governing energy homeostasis in lepidopteran larvae and may inform strategies for managing invasive pest species.

Keywords

energy homeostasis • gustatory receptors • neuropeptides • energy storage • nutrient sensing • invasive pest • fall webworm •
Hyphantria cunea