Trehalose metabolism regulates transcriptional control of muscle development in lepidopteran insects

The connection between trehalose metabolism and insect muscle development has long been unclear. Here we demonstrate that trehalose-derived glucose flux is essential for sustaining glycolysis and maintaining cellular energetics during metamorphosis in Helicoverpa armigera . Disruption of trehalose synthesis through silencing of trehalose 6-phosphate synthase/phosphatase ( TPS/TPP ) or paramyosin ( Prm ) produced defective eclosion and alike fragmented muscle fibers. Metabolic profiling revealed broad depletion of glycolytic intermediates and cofactors consistent with elevated AMP and activation of energy-stress signalling. Transcriptome analysis also showed downregulation of the transcription factor E2F/Dp , along with reduced expression of cyclin/CDK components, indicative of cell cycle checkpoint dysregulation. E2F/Dp repression resulted in lower expression of Mef2, Prm, MHC, and other sarcomeric components, causing defective muscle development and weakened muscle architecture. Gene set enrichment analysis, gene regulatory network and promotor binding analysis confirmed E2F binding motifs within promoters of trehalose metabolism and myogenic genes, suggesting a potential metabolic–transcriptional connection. Furthermore, dietary trehalose supplementation partially rescued metabolic depletion and restored expression of E2F targets in TPS/TPP - and E2F/Dp -silenced insects. Collectively, our findings establish trehalose metabolism as a metabolic regulator that couples energy homeostasis to cell-cycle transcriptional control and muscle development.