Monobutyl phthalate can induce autophagy and metabolic disorders by activating the ire1a-xbp1 pathway in zebrafish liver

Abstract

Monobutyl phthalate (MBP) can exist in biological organisms for a long time because of its excellent fat solubility, and it has been found to have certain toxic effects. In this study, the acute effects of MBP on endoplasmic reticulum (ER) stress and metabolism in the zebrafish liver were studied. After continuous exposure to MBP (5 and 10 mg / L) for 96 h, ER damage and the appearance of apoptotic bodies and autophagosomes were found in liver. This is because MBP stimulated the ire-xbp1 pathway of ER stress, thus leading to apoptosis and autophagy. Also, through analysis of metabolic enzymes and genes, it was found that the activated ire-xbp1 pathway could promote lipid synthesis and cause the accumulation of lipid droplets. The gene pparγ related to lipid storage affected the level of insulin, which can also further affect the glucose metabolism process, that is, glycolysis and aerobic respiration were inhibited. And the pentose phosphate pathway (PPP) was activated as a compensation mechanism to alleviate glycogen accumulation. The abnormal supply of energy and the death of excessive cells will eventually severely damage the zebrafish liver. This study will enrich the knowledge about the toxic effects of MBP.