Lipid-related metabolism during zebrafish embryogenesis under unbalanced copper homeostasis

Copper (Cu) is an essential trace element, playing an important role in lipid metabolism, and its transporters ATP7A and ATP7B, as Cu-transporting P-type ATPases, are involved in maintaining the Cu homeostasis in cells. Numerous studies in mammals have shown that Cu homeostasis and lipid metabolism are closely related, but studies on the link between the effects of excess Cu, ATP7A, and ATP7B on lipid metabolism during vertebrate embryogenesis are scarce. In this study, zebrafish disease models with Cu overload and ATP7A and ATP7B inactivation, respectively, were used to study the lipid metabolism-related differentially expressed genes (DEGs) which were enriched in the models. The dynamic and spatiotemporal expressions of the DEGs in WTs, atp7a^-/-, and atp7b^-/- mutants with or without Cu stress were unveiled in this study and they mostly distributed in brain at 24 hpf then in liver and intestine at 96 hpf, suggesting their potential roles in lipid and glycogen metabolism to apply energy for normal development in zebrafish. Meanwhile, the correlation analysis for the DEGs among the three groups unveiled that most of the DEGs were involved in the glyceride metabolism pathway. This is the first report to establish the relationship between atp7a and atp7b with Cu-stimulated intestinal and liver lipid metabolism during fish embryogenesis, and this study will provide a theoretical basis for fish embryonic development and lipid metabolism disorders under unbalanced copper homeostasis.