BR-C promotes lipid synthesis through the nuclear receptor HR96 during metamorphosis in insects

Insect metamorphosis needs substantial energy mobilization, and lipid serves as a crucial energy resource during the non-feeding pupal stage. The Broad Complex (BR-C) acts as a critical mediator of ecdysone signaling, which is the key regulator of insect metamorphosis. While the functions of BR-C in developmental transitions have been extensively characterized, its potential role in regulating lipid metabolism remains largely unexplored. Here, we demonstrate that BR-C is essential for lipid synthesis in the fat body during the larval-pupal transition. BR-C knockdown in both Bombyx and Drosophila resulted in significantly reduced lipid contents in the fat body and downregulated transcription of critical lipid synthase genes, including long-chain acyl-CoA synthetase (Acsl) and phosphatidic acid phosphatase (Lipin). We further identified the nuclear receptor gene HR96 as a direct target of BR-C and showed that HR96 knockdown phenocopied the reduced lipid synthesis that caused by BR-C knockdown. Mechanistically, we revealed that HR96 protein directly binds to the promoter regions of Acsl and Lipin to activate their transcription. Together, our findings establish a novel BR-C-HR96-lipid synthesis cascade that is functionally conserved in insects.