Simple SummaryThe liver transcriptome was analyzed after 22 d culture with different salinity water using RNA sequencing (RNA-seq) in spotted scat (Scatophagus argus). The genes involved in lipid metabolism were differentially down- or up-regulated in low (5 ppt)- and high (35 ppt)-salinity-rated fish in comparison with the control (25 ppt) group. The difference in liver lipid metabolism is important to adapt to low- and high-salinity stress in spotted scat, which has an important value for understanding the molecular basis of salinity adaptation in euryhaline fish.AbstractSpotted scat (Scatophagus argus) can tolerate a wide range of salinity fluctuations. It is a good model for studying environmental salinity adaptation. Lipid metabolism plays an important role in salinity adaptation in fish. To elucidate the mechanism of lipid metabolism in the osmoregulation, the liver transcriptome was analyzed after 22 d culture with a salinity of 5 ppt (Low-salinity group: LS), 25 ppt (Control group: Ctrl), and 35 ppt (High-salinity group: HS) water by using RNA sequencing (RNA-seq) in spotted scat. RNA-seq analysis showed that 1276 and 2768 differentially expressed genes (DEGs) were identified in the LS vs. Ctrl and HS vs. Ctrl, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the pathways of steroid hormone biosynthesis, steroid biosynthesis, glycerophospholipid metabolism, glycerolipid metabolism, and lipid metabolism were significantly enriched in the LS vs. Ctrl. The genes of steroid biosynthesis (sqle,dhcr7, andcyp51a1), steroid hormone biosynthesis (ugt2a1,ugt2a2,ugt2b20, andugt2b31), and glycerophospholipid metabolism (cept1,pla2g4a, andptdss2) were significantly down-regulated in the LS vs. Ctrl. The pathways related to lipid metabolisms, such as fatty acid metabolism, fatty acid biosynthesis, peroxisome proliferator-activated receptor (PPAR) signaling pathway, adipocytokine signaling pathway, fatty acid degradation, and unsaturated fatty acid biosynthesis, were significantly enriched in the HS vs. Ctrl. The genes of unsaturated fatty acid biosynthesis (scd1,hacd3,fads2,pecr, andelovl1) and adipocytokine signaling pathway (g6pc1,socs1,socs3,adipor2,pck1, andpparα) were significantly up-regulated in the HS vs. Ctrl. These results suggest that the difference in liver lipid metabolism is important to adapt to low- and high-salinity stress in spotted scat, which clarifies the molecular regulatory mechanisms of salinity adaptation in euryhaline fish.