Laboratory of Molecular Nutrition, Fishery College, Huazhong Agricultural University, Wuhan, 430070, China.
Laboratory of Molecular Nutrition, Fishery College, Huazhong Agricultural University, Wuhan, 430070, China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China.
Environ Pollut. 2020 Aug;263(Pt B):114420. doi: 10.1016/j.envpol.2020.114420. Epub 2020 Mar 27.
Lipid metabolism could be used as a biomarker for environmental monitoring of metal pollution, including Cu. Given the potential role of the Wnt/β-catenin signaling pathway and acetylation in lipid metabolism, the aim of this study was to investigate the mechanism of Wnt signaling and acetylation mediating Cu-induced lipogenesis. Grass carp Ctenopharyngodon idella, widely distributed freshwater teleost, were used as the model. We found that waterborne Cu exposure increased the accumulation of Cu and lipid, up-regulated lipogenesis, suppressed Wnt signaling, reduced β-catenin protein level and its nuclear location, reduced the sirt1 mRNA levels and up-regulated the β-catenin acetylation level. Further investigation found that Cu up-regulated lipogenesis through Wnt/β-catenin pathway; Cu regulated the β-catenin acetylation, and K311 was the key acetylated residue after Cu incubation. SIRT1 mediated Cu-induced changes of acetylated β-catenin and played an essential role in nuclear accumulation of β-catenin and Cu-induced lipogenesis. Cu facilitated lipid accumulation via the regulation of Wnt pathway by SIRT1. For the first time, our study uncovered the novel mechanism for Wnt/β-catenin pathway and β-catenin acetylation levels mediating Cu-induced lipid deposition, which provided insights into the association between Cu exposure and lipid metabolism in fish and had important environmental implications for monitoring metal pollution in the water by using new biomarkers involved in lipid metabolism.
脂质代谢可作为金属污染环境监测的生物标志物，包括铜。鉴于 Wnt/β-连环蛋白信号通路和乙酰化在脂质代谢中的潜在作用，本研究旨在探讨 Wnt 信号和乙酰化介导铜诱导脂肪生成的机制。广泛分布于淡水的鲤鱼（Ctenopharyngodon idella）被用作模型。我们发现，水相铜暴露会增加铜和脂质的积累，上调脂肪生成，抑制 Wnt 信号，降低β-连环蛋白蛋白水平及其核定位，降低 sirt1 mRNA 水平并上调β-连环蛋白乙酰化水平。进一步的研究发现，铜通过 Wnt/β-连环蛋白通路上调脂肪生成；铜调节β-连环蛋白乙酰化，K311 是铜孵育后关键的乙酰化残基。SIRT1 介导铜诱导的乙酰化β-连环蛋白变化，并在β-连环蛋白的核积累和铜诱导的脂肪生成中发挥重要作用。SIRT1 通过调节 Wnt 通路促进脂质积累。本研究首次揭示了 Wnt/β-连环蛋白通路和β-连环蛋白乙酰化水平介导铜诱导脂质沉积的新机制，为铜暴露与鱼类脂质代谢之间的关联提供了新的认识，并为利用涉及脂质代谢的新生物标志物监测水中金属污染具有重要的环境意义。
