Single-minded regulates larval energy homeostasis in the fall armyworm Spodoptera frugiperda

The Single-minded (Sim) gene encodes a conserved bHLH-PAS transcription factor that plays a critical role in neurodevelopment, yet its function in regulating insect growth and metabolism remains largely unexplored. In this study, we investigated the role of Sim in the growth and development of a major agricultural pest fall armyworm, Spodoptera frugiperda (SfSim). Using CRISPR/Cas9-mediated mutagenesis, we demonstrated that SfSim was essential for larval viability, as mosaic mutants displayed pronounced growth retardation. Integrated transcriptomic and biochemical analyses revealed that loss of SfSim disrupted carbohydrate and lipid metabolism, possibly associating with the impaired glucose homeostasis and a failure in lipid mobilization. Specifically, SfSim mutants accumulated excessive triglycerides due to dysregulated lipogenesis accompanied by suppressed lipolysis. This metabolic imbalance was further associated with a significant reduction in the expression of adipokinetic hormone (AKH) and its receptor AKHR. Collectively, our findings identify SfSim as a central regulator of larval metabolism and development in S. frugiperda, shedding light on the identification of novel potent targets for pest control measures.