Methionine restriction reduced growth performance and exacerbated lipid deposition in hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂) under high-lipid diets by suppressing the lipid degradation pathways with the single-cell RNA-seq an

The experiment mainly focused on the liver of the hybrid grouper ( Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂ ) with low methionine levels by single-cell RNA-seq under high-lipid diets. Both weight gain rate (WGR) and specific growth rate (SGR) in the MR group were obviously lower than the C group , and the intraperitoneal fat (IPF) in the MR group was obviously enhanced than HL and C groups , which led to more visible growth inhibition and lipid deposition. By using the scRNA-seq analysis, nine cell types were classified as: liver parenchymal cells, erythrocytes, hepatic stellate cells, cholangiocytes, macrophages, T cells, epidermal cells, eosinophil and fibroblasts. Lipid and carbohydrate metabolisms were mainly enriched in liver parenchymal cells. The lipid degradation pathways were obviously inhibited in the MR group, such as cholesterol degradation pathway. The lipid degradation genes were obviously decreased in the MR group. In conclusion, methionine restriction might suppress the lipid degradation pathways in liver parenchymal cells, led to obvious lipid deposition. • The methionine restriction diet could obviously lead to growth inhibition and more lipid deposition of fish fed high-lipid diets • Nine cell types subpopulation were classified in liver, including liver parenchymal cells, erythrocytes, hepatic stellate cells, cholangiocytes, macrophages, T cells, epidermal cells, eosinophil and fibroblasts. • Under high-lipid feeding, methionine restriction could suppress the cholesterol degradation pathway, the glycerolipid metabolism pathway and the linoleic acid metabolism pathway in liver parenchymal cells.