Hubei Hongshan Laboratory, Fishery College, Huazhong Agriculture University, Wuhan 430070, China.
Lady Davis Institute for Medical Research, Department of Medicine, McGill University, Montreal H3T 1E2, Quebec, Canada.
Biochim Biophys Acta Gene Regul Mech. 2022 Apr;1865(3):194802. doi: 10.1016/j.bbagrm.2022.194802. Epub 2022 Mar 4.
At present, studies involved in the effects of dietary Se sources on lipid metabolism were very scarce and the underlying mechanism remains unknown. Previous studies reported that dietary Se sources differentially affected selenoprotein S (SELENOS) expression and SELENOS affected lipid metabolism via the inositol-requiring enzyme 1α (IRE1α)- spliced X-box binding protein 1 (XBP1s) pathway. Thus, we used yellow catfish as an experimental model to explore whether dietary selenium sources affected the hepatic lipid metabolism, and further determined the role of SELENOS-IRE1α-XBP1s pathway in dietary selenium sources affecting hepatic lipid metabolism. Compared with the selenomethionine (S-M) group, sodium selenite (SS) group possessed higher liver triglycerides (TGs) (34.7%), lipogenic enzyme activities (57.9-70.6%), and lower antioxidant enzyme activities (23.3-35.5%), increased protein levels of heat shock transcription factor 1 (HSF1) and SELENOS (1.17-fold and 47.4%, respectively), and XBP1s- peroxisome proliferators-activated receptor γ (PPARγ) pathway. Blocking SELENOS and PPARγ by RNA interference demonstrated that the SELENOS/XBP1s/PPARγ axis was critical for S-S-induced lipid accumulation. Moreover, S-S-induced upregulation of SELENOS was via the increased DNA binding capacity of HSF1 to SELENOS promoter, which activated the XBP1s/PPARγ pathway and promoted lipogenesis and lipid accumulation. XBP1s is required for S-S-induced upregulation of PPARγ expression. Our finding elucidated the mechanism of dietary Se sources affecting the lipid metabolism in the liver of yellow catfish and demonstrated novel function of SELENOS in metabolic regulation. Our study also suggested that seleno-methionine was a better Se source than selenite against abnormal lipid deposition in the liver of yellow catfish.
目前，关于膳食硒源对脂质代谢影响的研究非常有限，其潜在机制尚不清楚。先前的研究报道，膳食硒源通过差异调节硒蛋白 S（SELENOS）的表达，而 SELENOS 通过肌醇需求酶 1α（IRE1α）-剪接 X 盒结合蛋白 1（XBP1s）途径影响脂质代谢。因此，我们使用黄颡鱼作为实验模型来探索膳食硒源是否影响肝脏脂质代谢，并进一步确定 SELENOS-IRE1α-XBP1s 途径在膳食硒源影响肝脏脂质代谢中的作用。与硒蛋氨酸（S-M）组相比，亚硒酸钠（SS）组肝脏甘油三酯（TGs）含量更高（34.7%），生脂酶活性更高（57.9-70.6%），抗氧化酶活性更低（23.3-35.5%），热休克转录因子 1（HSF1）和 SELENOS 蛋白水平更高（分别增加 1.17 倍和 47.4%），XBP1s-过氧化物酶体增殖物激活受体γ（PPARγ）途径激活。通过 RNA 干扰阻断 SELENOS 和 PPARγ 表明，SELENOS/XBP1s/PPARγ 轴对于 S-S 诱导的脂质积累至关重要。此外，S-S 诱导的 SELENOS 上调是通过增加 HSF1 与 SELENOS 启动子的 DNA 结合能力，激活 XBP1s/PPARγ 途径，促进生脂和脂质积累。XBP1s 是 S-S 诱导 PPARγ 表达上调所必需的。本研究阐明了膳食硒源影响黄颡鱼肝脂质代谢的机制，并证实了 SELENOS 在代谢调控中的新功能。本研究还表明，硒蛋氨酸是一种比亚硒酸钠更好的硒源，可以防止黄颡鱼肝中异常的脂质沉积。
