College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China.
Nansha-South China Agricultural University Fishery Research Institute, Guangzhou 510642, China.
Genes (Basel). 2024 Mar 4;15(3):334. doi: 10.3390/genes15030334.
Lipophagy is a selective autophagy that regulates lipid metabolism and reduces hepatic lipid deposition. However, the underlying mechanism has not been understood in fish. In this study, we used micronutrient zinc (Zn) as a regulator of autophagy and lipid metabolism and found that Ras-related protein 7 () was involved in Zn-induced lipophagy in hepatocytes of yellow catfish . We then characterized the promoter and identified binding sites for a series of transcription factors, including Forkhead box O3 (FOXO3). Site mutation experiments showed that the -1358/-1369 bp FOXO3 binding site was responsible for Zn-induced transcriptional activation of . Further studies showed that inhibition of significantly inhibited Zn-induced lipid degradation by lipophagy. Moreover, inhibitor also mitigated the Zn-induced increase of and expression. Our results suggested that Zn exerts its lipid-lowering effect partly through -mediated lipophagy and FA β-oxidation in hepatocytes. Overall, our findings provide novel insights into the FOXO3/ axis in lipophagy regulation and enhance the understanding of lipid metabolism by micronutrient Zn, which may help to reduce excessive lipid accumulation in fish.
脂噬作用是一种选择性自噬，可调节脂质代谢并减少肝脏脂质沉积。然而，鱼类中这一机制尚未得到阐明。在这项研究中，我们使用微量营养素锌（Zn）作为自噬和脂质代谢的调节剂，发现 Ras 相关蛋白 7 () 参与了黄色鲶鱼肝细胞中 Zn 诱导的脂噬作用。然后，我们对 启动子进行了表征，并鉴定了一系列转录因子的结合位点，包括 Forkhead box O3 (FOXO3)。位点突变实验表明，-1358/-1369 bp FOXO3 结合位点负责 Zn 诱导的 转录激活。进一步的研究表明，抑制 显著抑制了 Zn 诱导的脂噬作用引起的脂质降解。此外， 抑制剂也减轻了 Zn 诱导的 和 的表达增加。我们的结果表明，Zn 通过 - 介导的脂噬作用和肝细胞中的 FA β-氧化发挥其降脂作用。总的来说，我们的发现为 FOXO3/ 轴在脂噬作用调节中的作用提供了新的见解，并增强了对微量营养素 Zn 调节脂质代谢的理解，这可能有助于减少鱼类中过多的脂质积累。
