Copper nanoparticles induce the formation of fatty liver in Takifugu fasciatus triggered by the PERK-EIF2α-SREBP-1c pathway

Copper nanoparticles (CuNPs), a new pollutant in water environments, were widely used in various industrial and commercial applications. This study indicated that the presence of CuNPs exposure under environmental related concentration is an inducing factor that contributes to the fatty liver formation in Takifugu fasciatus. Furthermore, we explored the fatty liver formation mechanism. The results shown, (1) the cloned genes related to endoplasmic reticulum stress (ERS) (GRP78, IRE-1 alpha, PERK, and ATF-6 alpha) were highly expressed in the liver of T. fasciatus. (2) after 30-days exposure, CuNPs accumulated in the endoplasmic reticulum of liver and induced the appearance of ERS, then activated unfolded protein response (UPR) signaling pathway. Furthermore, the SREBP-1c pathway that plays a key role in lipid synthesis was activated. (3) by using 4-PBA and GSK inhibitors to respectively stimulate ERS and PKR-like ER kinase (PERK) through in vitro experiments, we confirmed that CuNPs induced the fatty liver formation in T. fasciatus triggered by the PERK-EIF2 alpha pathway by activating the SREBP-1c pathway to promote fatty liver formation. This study provides a new perspective for identifying the pathogens of fatty liver formation, and adds to the knowledge of the ecological safety data service of CuNPs in water

Automated summary

This study revealed that exposure to CuNPs at environmental-related concentrations can induce fatty liver formation in Takifugu fasciatus, mainly through endoplasmic reticulum stress and lipid synthesis pathways. The findings provide a new understanding of the mechanisms behind fatty liver formation and contribute to the ecological safety data on CuNPs in water environments.