Mitochondrial apoptotic pathway mediated the Zn-induced lipolysis in yellow catfish Peteobagrus fulvidraco

In the study, effects of waterborne zinc (Zn) exposure on apoptosis were investigated, and the potential mechanism of apoptosis participating in the Zn-induced variations of lipid metabolism was explored in a low vertebrate, yellow catfish Pelteobagrus fulvidraco. We found that Zn induced occurrence of apoptosis of livers and hepatocytes in yellow catfish. Waterborne Zn also increased hepatic transcriptional levels of p53, cytochrome c (Cycs), caspase 3a (Casp3a) and caspase 3b (Casp3b) of yellow catfish. Zn increased caspase 3 activity and reduced the mitochondrial permeability transition (MTP) in yellow catfish hepatocytes. Z-VAD-fmk (caspase inhibitor) and CsA pretreatment (MTP inhibitor) attenuated the Zn-induced apoptosis and reduction in MTP. Z-VAD-fmk pretreatments attenuated the Zn-induced increase in transcriptional levels of p53, Cycs and Casp3b although the differences were not statistically significant between the Zn group and Zn + Z-VAD-fmk group. In contrast, Zn and N-acetylcysteine (NAC) did not significantly influence the reactive oxygen species (ROS) production. Zn significantly reduced triglyceride (TG) content, increased the activities of carnitine palmitoyltransferase 1 (CPT I), hormone-sensitive lipase (HSL) and adipose TAG lipase (ATGL), and the transcriptional levels of p53, Cycs and caspase 3b of the hepatocytes; these Zn-induced effects on TG contents, activities of CPT I, HSL and ATGL, and mRNA levels of p53, Cycs and caspase 3b could partly be reversed by Z-VAD-fmk, suggesting that Zn induced the mitochondrial-mediated apoptosis and reduced lipid accumulation. Taken together, our study demonstrated the importance of mitochondria-mediated apoptosis in Zn-induced lipolysis, which suggested a new mechanism for elucidating metal element influencing lipid metabolism.