锌通过 Beclin1 的去乙酰化诱导脂肪吞噬，并在其环境相关浓度下减轻铜诱导的脂毒性,Environmental Science & Technology

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锌通过 Beclin1 的去乙酰化诱导脂肪吞噬，并在其环境相关浓度下减轻铜诱导的脂毒性
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2021-03-19 , DOI: 10.1021/acs.est.0c08609
Xiaolei Wei ₁ , Christer Hogstrand ₂ , Guanghui Chen ₁ , Wuhong Lv ₁ , Yufeng Song ₁ , Yichuang Xu ₁ , Zhi Luo ₁

Affiliation

在本研究中，研究了环境相关剂量的 Cu 和 Zn 混合物影响淡水硬骨黄鲶的脂质沉积和代谢的机制Pelteobagrus fulvidraco这些研究结果表明，锌诱导的 Beclin1 去乙酰化促进了脂肪吞噬，这是减轻铜诱导的鱼类脂质积累的重要途径，这揭示了一种以前未知的机制，可以理解铜和锌在其环境相关浓度下对代谢的拮抗作用。我们的研究结果强调了在环境风险评估期间评估重金属的生物效应时综合暴露的重要性。

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Zn Induces Lipophagy via the Deacetylation of Beclin1 and Alleviates Cu-Induced Lipotoxicity at Their Environmentally Relevant Concentrations

In this study, the mechanisms of environmentally relevant doses of Cu and Zn mixtures influencing lipid deposition and metabolism were investigated in freshwater teleost yellow catfish Pelteobagrus fulvidraco (2 months old, 4.95 (t0.01 g, mean ± SEM). Our study indicated that waterborne Cu exposure increased lipid content, while Zn activated lipophagic flux and alleviated Cu-induced lipid accumulation. Yellow catfish hepatocytes treated with Zn or Zn + Cu activated autophagy-specific lipophagy, decreased lipid storage, and increased nonesterified fatty acid (NEFA) release, suggesting a causal relationship between lipophagy and lipid droplet (LD) breakdown under Zn and Zn + Cu conditions. Our further investigation found that Beclin1 deacetylation by sirtuin 1 (SIRT1) was required for Zn- and Zn + Cu-induced lipophagy and lipolysis, and lysine residues 427 and 434 were key sites for Beclin1 deacetylation. Taken together, these findings show that the Zn-induced deacetylation of Beclin1 promotes lipophagy as an important pathway to alleviate Cu-induced lipid accumulation in fish, which reveals a previously unidentified mechanism for understanding the antagonistic effects of Cu and Zn on metabolism at their environmentally relevant concentrations. Our results highlight the importance of combined exposure when the biological effects of heavy metals are evaluated during environmental risk assessments.

更新日期：2021-04-20

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