Department of Nutritional Sciences, University of Wisconsin, Madison, Wisconsin, United States of America.
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota, United States of America.
PLoS One. 2020 May 7;15(5):e0232160. doi: 10.1371/journal.pone.0232160. eCollection 2020.
There is interest in supplementing animals and humans with selenium (Se) above Se-adequate levels, but the only good biomarker for toxicity is tissue Se. We targeted liver because turkeys fed 5 μg Se/g have hepatic Se concentrations 6-fold above Se-adequate (0.4 μg Se/g) levels without effects on growth or health. Our objectives were (i) to identify transcript biomarkers for high Se status, which in turn would (ii) suggest proteins and pathways used by animals to adapt to high Se. Turkey poults were fed 0, 0.025, 0.4, 0.75 and 1.0 μg Se/g diet in experiment 1, and fed 0.4, 2.0 and 5.0 μg Se/g in experiment 2, as selenite, and the full liver transcriptome determined by RNA-Seq. The major effect of Se-deficiency was to down-regulate expression of a subset of selenoprotein transcripts, with little significant effect on general transcript expression. In response to high Se intake (2 and 5 μg Se/g) relative to Se-adequate turkeys, there were only a limited number of significant differentially expressed transcripts, all with only relatively small fold-changes. No transcript showed a consistent pattern of altered expression in response to high Se intakes across the 1, 2 and 5 μg Se/g treatments, and there were no associated metabolic pathways and biological functions that were significant and consistently found with high Se supplementation. Gene set enrichment analysis also found no gene sets that were consistently altered by high-Se and supernutritional-Se. A comparison of differentially expressed transcript sets with high Se transcript sets identified in mice provided high Se (~3 μg Se/g) also failed to identify common differentially expressed transcript sets between these two species. Collectively, this study indicates that turkeys do not alter gene expression in the liver as a homeostatic mechanism to adapt to high Se.
人们对在硒(Se)充足水平以上补充动物和人类硒(Se)很感兴趣,但毒性的唯一良好生物标志物是组织硒(Se)。我们以肝脏为目标,因为给食用 5 μg Se/g 的火鸡喂食,其肝脏硒(Se)浓度是硒(Se)充足(0.4 μg Se/g)水平的 6 倍,且对生长或健康没有影响。我们的目标是:(i)确定高硒(Se)状态的转录生物标志物,这反过来将(ii)提示动物用来适应高硒(Se)的蛋白质和途径。在实验 1 中,火鸡雏鸡分别以 0、0.025、0.4、0.75 和 1.0 μg Se/g 饮食的亚硒酸钠喂食,在实验 2 中,以 0.4、2.0 和 5.0 μg Se/g 喂食,然后通过 RNA-Seq 确定整个肝脏转录组。硒(Se)缺乏的主要影响是下调一组硒蛋白转录物的表达,对一般转录物表达几乎没有显著影响。与硒(Se)充足的火鸡相比,对高硒(Se)摄入(2 和 5 μg Se/g)的反应仅表现为少数有显著差异的表达转录物,所有转录物的倍数变化都相对较小。在高硒(Se)摄入(1、2 和 5 μg Se/g)下,没有一个转录物显示出一致的表达模式,高硒(Se)补充也没有发现显著且一致的代谢途径和生物学功能。基因集富集分析也没有发现高硒(Se)和超营养硒(Se)一致改变的基因集。与高 Se 转录组比较,差异表达转录组与高 Se 转录组的比较发现,高 Se(~3 μg Se/g)也未能在这两个物种之间确定共同的差异表达转录组。总的来说,这项研究表明,火鸡不会改变肝脏中的基因表达作为适应高硒(Se)的体内平衡机制。