Unraveling nutritional regulation mechanisms in Bombyx mori : how an artificial diet impairs silk synthesis by inducing dysfunctional energy metabolism

Bombyx mori (Lepidoptera: Bombycidae) silk proteins are highly valued materials for textile and biomaterial applications. Currently, the molecular mechanisms underlying the nutritional regulation of silk synthesis have not yet been systematically elucidated. Low silk yields persist and cause bottlenecks, hindering the industrial application of artificial diet sericulture. This study integrated hemolymph metabolomics and silk gland transcriptomics to investigate the key factors contributing to reduced silk yields in silkworms fed an artificial diet when compared to worms fed mulberry leaves, and to explore the nutritional regulatory mechanisms enhancing efficient silk synthesis. We showed that an artificial diet al.ered silkworm energy metabolism in late fifth instar stages, upregulating key energy metabolism genes (eg ATP synthase, cytochrome c oxidase, NADH dehydrogenase, and hypoxia-upregulated protein) in silk glands, and increasing hemolymph lactic acid levels. The artificial diet al.o elevated most hemolymph amino acids, their metabolites, and sugars (eg trehalose, sorbose, glucose, and mannose), indicating adequate protein and carbohydrate supply. Further analysis showed that increasing oxygen levels optimized energy metabolism, effectively reducing accumulation of the anaerobic byproduct lactic acid and enhancing silk yields. Therefore, the low energy utilization efficiency of an artificial diet is a key limiting factor affecting silk yields; therefore, optimizing silk gland energy metabolism is critical for enhancing silk synthesis.