TY - JOUR
T1 - Manganese triggers hepatic lipotoxicity via mitochondrial oxidative stress-dependent HSF1/PPARg pathway in a freshwater teleost
AU - Chen, Guang-Hui
AU - Song, Chang-Chun
AU - Zhao, Tao
AU - Hogstrand, Christer
AU - Wei, Xiao-Lei
AU - Lv, Wu-Hong
AU - Song, Yu Feng
AU - Luo, Zhi
PY - 2022/1/25
Y1 - 2022/1/25
N2 - Due to many special characteristics, zinc oxide nanoparticles (ZnO NPs) are widely used all over the world, leading to their wide distribution in the environment. However, the toxicities and mechanisms of environmental ZnO NPs-induced changes of physiological processes and metabolism remain largely unknown. Here, we found that dietary ZnO NPs addition disturbed hepatic Zn metabolism, increased hepatic Zn and lipid accumulation, and down-regulated lipolysis, induced oxidative stress and activated mitophagy; N, N, N', N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN, Zn2+ ions chelator) alleviated high ZnO NPs-induced Zn and lipid accumulation, oxidative stress and mitophagy. Mechanistically, the suppression of mitochondrial oxidative stress attenuated ZnO NPs-activated mitophagy and ZnO NPs-induced lipotoxicity. Taken together, our study elucidated that mitochondrial oxidative stress mediated ZnO NPs-induced mitophagy and lipotoxicity; ZnO NPs could be dissociated to free Zn2+ ions, which partially contributed to ZnO NPs-induced changes in oxidative stress, mitophagy and lipid metabolism. Our study provides the novel insights into the impacts and mechanism of ZnO NPs as harmful substances inducing lipotoxicity of aquatic organisms, and accordingly the metabolism-relevant parameters will be useful for the risk assessment of nanoparticle materials in the environment.
AB - Due to many special characteristics, zinc oxide nanoparticles (ZnO NPs) are widely used all over the world, leading to their wide distribution in the environment. However, the toxicities and mechanisms of environmental ZnO NPs-induced changes of physiological processes and metabolism remain largely unknown. Here, we found that dietary ZnO NPs addition disturbed hepatic Zn metabolism, increased hepatic Zn and lipid accumulation, and down-regulated lipolysis, induced oxidative stress and activated mitophagy; N, N, N', N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN, Zn2+ ions chelator) alleviated high ZnO NPs-induced Zn and lipid accumulation, oxidative stress and mitophagy. Mechanistically, the suppression of mitochondrial oxidative stress attenuated ZnO NPs-activated mitophagy and ZnO NPs-induced lipotoxicity. Taken together, our study elucidated that mitochondrial oxidative stress mediated ZnO NPs-induced mitophagy and lipotoxicity; ZnO NPs could be dissociated to free Zn2+ ions, which partially contributed to ZnO NPs-induced changes in oxidative stress, mitophagy and lipid metabolism. Our study provides the novel insights into the impacts and mechanism of ZnO NPs as harmful substances inducing lipotoxicity of aquatic organisms, and accordingly the metabolism-relevant parameters will be useful for the risk assessment of nanoparticle materials in the environment.
M3 - Article
SN - 0013-936X
JO - Environmental science & technology
JF - Environmental science & technology
ER -