Progress 10/01/19 to 09/30/20
Outputs
Target Audience:This project focused on developing tissue mRNA levels as molecular biomarkers of nutrient status, using Se regulation of selenoprotein mRNAs in RNA from whole blood and other tissues as an example. This project is also determined dietary Se requirements for turkeys and assessing the safety of higher levels of Se supplementation. These studies have broad implications for small animal and large animal nutrition, as well as human nutrient assessment. The novel new identification of selenosugars as biomarkers of Se status, especially excess Se, is huge. Thus, the target audience for this work includes fellow researchers, producers and farmers, and the feed industry, but also government agencies and other bodies involved in setting nutrient requirements for animals and humans. Changes/Problems:In the studies, we found that liver Se in turkey poults fed 5 μg Se/g diet as Na2SeO3 increased 6-fold as compared to turkeys fed Se-adequate diet (0.4 μg Se/g), but that this increased Se was not due to increases of Se in selenoproteins or accompanied by changes in transcript expression. Thus, we are now studying the nature of the Se species that accumulate in avians and mammals fed high Se, using HPLC-ICP-MS and HPLC-ESI-MS/MS. This research may identify potential biomarkers for high Se status and help to determine upper limits for dietary Se supplementation. What opportunities for training and professional development has the project provided?A graduate student is being trained through this project and is seeking an advance degree in nutritional sciences so that she could take graduate classes and conduct the outlined studies. How have the results been disseminated to communities of interest?See Products and Other Products What do you plan to do during the next reporting period to accomplish the goals?In the next period, we will continue to analyze the low molecular weight Se metabolites in turkeys fed high Se, and this work will expand to look for selenosugar metabolites in rats as a model for humans and higher animals, to better understand Se toxicity and to potentially identify biomarkers for high Se status.
Impacts
What was accomplished under these goals?
There is increasing interest in supplementing animals and humans with selenium (Se) at dietary levels above those that raise selenoproteins to Se-adequate plateau levels. The only quantifiable biomarker for Se toxicity, however, currently appears to be tissue Se, which does not plateau. We targeted the liver because turkey poults fed 5 μg Se/g have hepatic Se concentrations 6-fold above levels in poults fed Se-adequate diet (0.4 μg Se/g as selenite) but without apparent effects on growth or health. To assess the full turkey transcriptome for the effect of Se status from Se-deficient to high-Se, we conducted RNA-Seq analysis on liver mRNA from turkey poults 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. Our objectives were (1) to identify transcript biomarkers for high Se status, which in turn would (2) suggest proteins and pathways used by animals to adapt to high Se. In publications reported this year, the major effect of Se-deficiency was to down-regulate expression of a subset of selenoprotein transcripts in liver, 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, 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. A comparison of differentially expressed transcript sets with high Se transcript sets identified in parallel studies in rats fed 2 and 5 μg Se/g, or by gene set enrichment analysis, also failed to identify common differentially expressed transcripts between these two species. Collectively, these studies indicate that neither avians nor mammals alter gene expression as a homeostatic mechanism to adapt to high Se. This work was published in PloSOne and J. of Nutrition. In collaboration with the CNRS/UPPA, Institute for Analytical Sciences and Physical Chemistry for the Environment and Materials (IPREM), in Pau, France, we characterized and quantitated the low molecular weight species of Se that accumulate in turkeys fed high inorganic Se using HPLC followed by ICP tandem MS. These analyses showed for the first time that supplementation of a monogastric animal with inorganic Se(IV) leads to the synthesis of only selenocysteine, with no synthesis of selenomethionine. In high Se turkey liver, excess Se(IV) is metabolized to selenosugar (SeGalNac) which reacts with low molecular weight thiols and with cysteine-containing peptides and proteins present in liver. These "selenosugar-decorated" proteins account for half of liver Se in Se-adequate as well as high-Se turkey liver. Conversion of Se to selenosugar to form glutathionyl-SeGalNac and methyl-SeGalNac has been well-reported, but our new finding is that "selenosugar-decorated" proteins can account for half or more of the Se in Se-adequate and high-Se liver, at least in the turkey. These selenosugar metabolites have potential to be excellent biomarkers for high Se status in animals and humans. This work was published in Metallomics.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Taylor RM, Mendoza KM, Abrahante JE, Reed KM, Sunde RA. 2020. The hepatic transcriptome of the turkey poult (Meleagris gallopavo) is minimally altered by high inorganic dietary selenium. PLoS One 15: e0232160. PMID: 32379770
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Bierla K, Taylor RM, Szpunar J, Lobinski R, Sunde RA. 2020. Identification and determination of selenocysteine, selenosugar, and other selenometabolites in turkey liver. Metallomics 12: 758-766. PMID: 32211715
- Type:
Book Chapters
Status:
Published
Year Published:
2020
Citation:
Sunde RA. 2020. Impact of high dietary selenium on the selenoprotein transcriptome, selenoproteome, and selenometabolites in multiple species. In: Selenium Research for Environment and Human Health: Perspectives, Technologies and Advancements (Banuelos G., Lin Z. Q., Liang D. & Yin X. B., eds.), pp. 159-160. Taylor and Francis, London
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2020
Citation:
Sunde RA, Taylor RM. 2020. Impact of high dietary selenium on the transcriptome and selenometabolites in turkeys. Plant Anim Genom. XXVIII: W882 (abs.)
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2020
Citation:
Sunde RA, Bierla K, Taylor RM, Szpunar J, Lobinski R. 2020. Selenosugars are the major selenometabolites in liver of turkeys fed high selenium. Curr Dev Nutr. 4 (Suppl 2): 1840. doi.org/10.1093/cdn/nzaa067_067 (abs)
- Type:
Journal Articles
Status:
Awaiting Publication
Year Published:
2020
Citation:
Sunde RA. 2020. Gene set enrichment analysis of selenium-deficient and high-selenium rat liver transcript expression and comparison with turkey liver expression. J Nutr. Accepted 10/1/20 PMID: 33245116 DOI: 10.1093/jn/nxaa333
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Progress 10/01/18 to 09/30/19
Outputs
Target Audience:The potential to develop quick and relatively inexpensive means to assess nutrient status on an individual basis, and to provide and monitor therapy is huge. Thus, the target audience for this work includes fellow researchers, producers and farmers, and the feed industry, but also government agencies and other bodies involved in setting nutrient requirements for animals and humans. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?This grant provided support for a graduate student seeking an advance degree in nutritional sciences. How have the results been disseminated to communities of interest?See products-Results were submitted to several journals and one thesis dissertation. What do you plan to do during the next reporting period to accomplish the goals?In the next period, we will continue to complete the RNA-Seq analysis of turkeys fed graded levels of Se from Se-deficient to high-Se. In addition we will begin to analyze the low molecular weight Se metabolites in turkeys fed high Se to better understand why turkeys are less susceptible to Se toxicity and to potentially identify biomakers for high Se status.
Impacts
What was accomplished under these goals?
There is increasing interest in supplementing animals and humans with selenium (Se) at dietary levels above those that raise selenoproteins to Se-adequate plateau levels. The only quantifiable biomarker for Se toxicity, however, currently appears to be tissue Se, which does not plateau. We targeted the liver because turkey poults fed 5 μg Se/g have hepatic Se concentrations 6-fold above levels in poults fed Se-adequate diet (0.4 μg Se/g as selenite) but without apparent effects on growth or health. To assess the full turkey transcriptome for the effect of Se status from Se-deficient to high-Se, we conducted RNA-Seq analysis on liver mRNA from turkey poults 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. Our objectives were (1) to identify transcript biomarkers for high Se status, which in turn would (2) suggest proteins and pathways used by animals to adapt to high Se. As reported previously, the major effect of Se-deficiency was to down-regulate expression of a subset of selenoprotein transcripts in liver, 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. A comparison of differentially expressed transcript sets with high Se transcript sets identified in parallel studies in rats (2 μg Se/g) or in mice (~3 μg Se/g) fed high Se also failed to identify common differentially expressed transcripts between these three species. Gene set enrichment analysis also found no gene sets that were consistently altered by high-Se and supernutritional-Se. Collectively, this study indicates that turkeys do not alter gene expression as a homeostatic mechanism to adapt to high Se. Targeting the nature of metabolites present in liver of turkeys fed high Se has the potential to identify biomarkers for high Se status and to suggest metabolic pathways used by turkeys to adapt to high Se intake. We found that liver Se in poults fed 5 μg Se/g diet as Na2SeO3 increased 6-fold as compared to turkeys fed Se-adequate diet (0.4 μg Se/g), but that this increased Se was not due to increases of Se in selenoproteins. Thus, we have begun to study the nature of the Se species that accumulate in animals fed high Se, using HPLC-ICP-MS and HPLC-ESI-MS/MS in collaborative studies. This research may identify potential biomarkers for high Se status and help to determine upper limits for dietary Se supplementation.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Taylor RM, Bourget VG, Sunde RA. 2019. High dietary inorganic selenium has minimal effects on turkeys and selenium status biomarkers. Poult. Sci. 98: 855-865. PMID: 30239950
- Type:
Theses/Dissertations
Status:
Accepted
Year Published:
2019
Citation:
Taylor RM. 2019. Response to high inorganic selenium in hepatic turkey selenoproteome, transcriptome and selenmetabolome. University of Wisconsin-Madison, PhD Dissertation.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Taylor RM, Sunde RA. 2019. Transcriptomic analysis of selenium-deficient and high-selenium turkey liver. Plant Anim Genom. PE0428. (abs.)
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Taylor RM, Sunde RA. 2019. Full transcriptome expression in liver of selenium-deficient and high-selenium turkeys (Meleagris gallopavo) determined by RNA-seq. ASN P24-025-19: (abs.)
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Taylor RM, Sunde RA. 2019. Selenium requirement of turkeys based on tissue selenium concentration and selenoprotein activity and transcript expression. J Anim Sci. 97: 177-178. (abs.)
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2019
Citation:
Sunde RA, Taylor RM. 2019. The Turkey Selenoproteome: genes and regulation of transcript expression by selenium deficiency and high Se status. Plant Anim Genom. 27: W881. (abs.)
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