Abstract
Broiler chicks are fast-growing and susceptible to dietary selenium (Se) deficiency. This study sought to reveal the underlying mechanisms of how Se deficiency induces key organ dysfunctions in broilers. Day-old male chicks (n=6 cages/diet, 6 chicks/cage) were fed with a Se-deficient diet (Se-Def, 0.047 mg Se/kg) or the Se-Def+0.3 mg Se/kg (Control, 0.345 mg Se/kg) for 6 weeks. The serum, liver, pancreas, spleen, heart, and pectoral muscle of the broilers were collected at week 6 to assay for Se concentration, histopathology, serum metabolome, and tissue transcriptome. Compared with the Control group, Se deficiency induced growth retardation and histopathological lesions and reduced Se concentration in the five organs. Integrated transcriptomics and metabolomics analysis revealed that dysregulation of immune and redox homeostasis related biological processes and pathways contributed to Se deficiency-induced multiple tissue damage in the broilers. Meanwhile, four metabolites in the serum, daidzein, epinephrine, L-aspartic acid and 5-hydroxyindoleacetic acid, interacted with differentially expressed genes with antioxidative effects and immunity among all the five organs, which contributed to the metabolic diseases induced by Se deficiency. Overall, this study systematically elucidated the underlying molecular mechanisms in the pathogenesis of Se deficiency-related diseases, which provides a better understanding of the significance of Se-mediated heath in animals.
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The datasets used and/or analyzed in the present study are publicly available.
References
Ammerman, C.B., and Miller, S.M. (1975). Selenium in ruminant nutrition: a review. J Dairy Sci 58, 1561–1577.
Bao, B., Kang, Z., Zhang, Y., Li, K., Xu, R., and Guo, M. (2022). Selenium deficiency leads to reduced skeletal muscle cell differentiation by oxidative stress in mice. Biol Trace Elem Res, doi: https://doi.org/10.1007/s12011-022-03288-2.
Birsoy, K., Wang, T., Chen, W.W., Freinkman, E., Abu-Remaileh, M., and Sabatini, D.M. (2015). An essential role of the mitochondrial electron transport chain in cell proliferation is to enable aspartate synthesis. Cell 162, 540–551.
Braganza, J.M. (1985). Selenium deficiency, cystic fibrosis, and pancreatic cancer. Lancet 326, 1238.
Bunk, M.J., and Combs, Jr. G.F. (1980). Effect of selenium on appetite in the selenium-deficient chick. J Nutr 110, 743–749.
Cao, J., Jin, Q., Wang, G., Dong, H., Feng, Y., Tian, J., Yun, K., Wang, Y., and Sun, J. (2018). Comparison of the serum metabolic signatures based on 1H NMR between patients and a rat model of deep vein thrombosis. Sci Rep 8, 7837.
Dam, H., Prange, I., and Sondergaard, E. (1955). Influence of various levels of dietary cholesterol on the cholesterol content of certain organs and of bile of chicks fed fat-free and peanut oil containing diets. Acta Physiol Scandinav 34, 141–146.
El-Sharawy, M.E., Hamouda, M., Soliman, A.A., Amer, A.A., El-Zayat, A. M., Sewilam, H., Younis, E.M., Abdel-Warith, A.W.A., and Dawood, M.A.O. (2021). Selenium nanoparticles are required for the optimum growth behavior, antioxidative capacity, and liver wellbeing of Striped catfish (Pangasianodon hypophthalmus). Saudi J Biol Sci 28, 7241–7247.
Foti, P., Erba, D., Riso, P., Spadafranca, A., Criscuoli, F., and Testolin, G. (2005). Comparison between daidzein and genistein antioxidant activity in primary and cancer lymphocytes. Arch Biochem Biophys 433, 421–427.
Guo, Q., Li, F., Duan, Y., Wen, C., Wang, W., Zhang, L., Huang, R., and Yin, Y. (2020). Oxidative stress, nutritional antioxidants and beyond. Sci China Life Sci 63, 866–874.
He, X., Lin, Y., Lian, S., Sun, D., Guo, D., Wang, J., and Wu, R. (2020). Selenium deficiency in chickens induces intestinal mucosal injury by affecting the mucosa morphology, SIgA secretion, and GSH-Px activity. Biol Trace Elem Res 197, 660–666.
He, Y., Niu, W., Xia, C., and Cao, B. (2016). Daidzein reduces the proliferation and adiposeness of 3T3-L1 preadipocytes via regulating adipogenic gene expression. J Funct Foods 22, 446–453.
Huang, J.Q., Li, D.L., Zhao, H., Sun, L.H., Xia, X.J., Wang, K.N., Luo, X., and Lei, X.G. (2011). The selenium deficiency disease exudative diathesis in chicks is associated with downregulation of seven common selenoprotein genes in liver and muscle. J Nutr 141, 1605–1610.
Huang, J.Q., Ren, F.Z., Jiang, Y.Y., Xiao, C., and Lei, X.G. (2015). Selenoproteins protect against avian nutritional muscular dystrophy by metabolizing peroxides and regulating redox/apoptotic signaling. Free Radical Biol Med 83, 129–138.
Huang, Y.C., Wu, T.L., Zeng, H., and Cheng, W.H. (2021). Dietary selenium requirement for the prevention of glucose intolerance and insulin resistance in middle-aged mice. J Nutr 151, 1894–1900.
Jarosz, M., Olbert, M., Wyszogrodzka, G., Młyniec, K., and Librowski, T. (2017). Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-κB signaling. Inflammopharmacology 25, 11–24.
Jia, M., Qin, D., Zhao, C., Chai, L., Yu, Z., Wang, W., Tong, L., Lv, L., Wang, Y., Rehwinkel, J., et al. (2020). Redox homeostasis maintained by GPX4 facilitates STING activation. Nat Immunol 21, 727–735.
John, J.L. (1994). The avian spleen: a neglected organ. Q Rev Biol 69, 327–351.
Karnovsky, A., Weymouth, T., Hull, T., Tarcea, V.G., Scardoni, G., Laudanna, C., Sartor, M.A., Stringer, K.A., Jagadish, H.V., Burant, C., et al. (2012). Metscape 2 bioinformatics tool for the analysis and visualization of metabolomics and gene expression data. Bioinformatics 28, 373–380.
Kim, D., Langmead, B., and Salzberg, S.L. (2015). HISAT: a fast spliced aligner with low memory requirements. Nat Methods 12, 357–360.
Lai, J.M., Zhang, X., Liu, F.F., Yang, R., Li, S.Y., Zhu, L.B., Zou, M., Cheng, W.H., and Zhu, J.H. (2016). Redox-sensitive MAPK and Notch3 regulate fibroblast differentiation and activation: a dual role of ERK1/2. Oncotarget 7, 43731–43745.
Lamkanfi, M., and Kanneganti, T.D. (2012). Regulation of immune pathways by the NOD-like receptor NLRC5. Immunobiology 217, 13–16.
Lee, H.S., Kim, S.M., Jang, J.H., Park, H.D., and Lee, S.Y. (2021). Serum 5-hydroxyindoleacetic acid and ratio of 5-hydroxyindoleacetic acid to serotonin as metabolomics indicators for acute oxidative stress and inflammation in vancomycin-associated acute kidney injury. Antioxidants 10, 895.
Lei, X.G., CombsJr., G.F., Sunde, R.A., Caton, J.S., Arthington, J.D., and Vatamaniuk, M.Z. (2022). Dietary selenium across species. Annu Rev Nutr 42, 337–375.
Li, N., Gao, Z., Luo, D., Tang, X., Chen, D., and Hu, Y. (2007). Selenium level in the environment and the population of Zhoukoudian area, Beijing, China. Sci Total Environ 381, 105–111.
Li, S., Zhao, Q., Zhang, K., Sun, W., Li, J., Guo, X., Yin, J., Zhang, J., and Tang, C. (2021). Selenium deficiency-induced pancreatic pathology is associated with oxidative stress and energy metabolism disequilibrium. Biol Trace Elem Res 199, 154–165.
Li, S., Sun, W., Zhang, K., Zhu, J., Jia, X., Guo, X., Zhao, Q., Tang, C., Yin, J., and Zhang, J. (2021). Selenium deficiency induces spleen pathological changes in pigs by decreasing selenoprotein expression, evoking oxidative stress, and activating inflammation and apoptosis. J anim Sci Biotechnol 12, 65.
Liao, X., Lu, L., Li, S., Liu, S., Zhang, L., Wang, G., Li, A., and Luo, X. (2012). Effects of selenium source and level on growth performance, tissue selenium concentrations, antioxidation, and immune functions of heat-stressed broilers. Biol Trace Elem Res 150, 158–165.
Liao, Y., Smyth, G.K., and Shi, W. (2014). featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923–930.
Liu, X., Suzuki, N., Santosh Laxmi, Y.R., Okamoto, Y., and Shibutani, S. (2012). Anti-breast cancer potential of daidzein in rodents. Life Sci 91, 415–419.
Loscalzo, J. (2014). Keshan disease, selenium deficiency, and the selenoproteome. N Engl J Med 370, 1756–1760.
Luan, D., Zhao, Z., Xia, D., Zheng, Q., Gao, X., Xu, K., and Tang, B. (2021). Hydrogen selenide, a vital metabolite of sodium selenite, uncouples the sulfilimine bond and promotes the reversal of liver fibrosis. Sci China Life Sci 64, 443–451.
McKenzie, B.S., Kastelein, R.A., and Cua, D.J. (2006). Understanding the IL-23−IL-17 immune pathway. Trends Immunol 27, 17–23.
Luca, S.V., Macovei, I., Bujor, A., Miron, A., Skalicka-Woźniak, K., Aprotosoaie, A.C., and Trifan, A. (2020). Bioactivity of dietary polyphenols: the role of metabolites. Crit Rev Food Sci Nutr 60, 626–659.
Merrill, Jr. A.H., Sullards, M.C., Wang, E., Voss, K.A., and Riley, R.T. (2001). Sphingolipid metabolism: roles in signal transduction and disruption by fumonisins.. Environ Health Perspect 109, 283–289.
Mittal, R., Debs, L.H., Patel, A.P., Nguyen, D., Patel, K., O’Connor, G., Grati, M., Mittal, J., Yan, D., Eshraghi, A.A., et al. (2017). Neurotransmitters: the critical modulators regulating gut-brain axis. J Cell Physiol 232, 2359–2372.
Oropeza-Moe, M., Wisløff, H., and Bernhoft, A. (2015). Selenium deficiency associated porcine and human cardiomyopathies. J Trace Elem Med Biol 31, 148–156.
Patel, D., Menon, D., Bernfeld, E., Mroz, V., Kalan, S., Loayza, D., and Foster, D.A. (2016). Aspartate rescues S-phase arrest caused by suppression of glutamine utilization in KRas-driven cancer cells. J Biol Chem 291, 9322–9329.
Purswell, J.L., Dozier, W.A., Olanrewaju, H.A., Davis, J.D., Xin, H. (2012). Effect of temperature-humidity index on live performance in broiler chickens grown from 49 to 63 days of age. In: the Ninth International Livestock Environment Symposium Valencia, Spain.
Rayman, M.P. (2012). Selenium and human health. Lancet 379, 1256–1268.
Safdari-Rostamabad, M., Hosseini-Vashan, S.J., Perai, A.H., and Sarir, H. (2017). Nanoselenium supplementation of heat-stressed broilers: effects on performance, carcass characteristics, blood metabolites, immune response, antioxidant status, and jejunal morphology. Biol Trace Elem Res 178, 105–116.
Schoors, S., Bruning, U., Missiaen, R., Queiroz, K.C.S., Borgers, G., Elia, I., Zecchin, A., Cantelmo, A.R., Christen, S., Goveia, J., et al. (2015). Fatty acid carbon is essential for dNTP synthesis in endothelial cells. Nature 520, 192–197.
Sun, H., Zhao, L., Xu, Z.J., De Marco, M., Briens, M., Yan, X.H., and Sun, L.H. (2021). Hydroxy-selenomethionine improves the selenium status and helps to maintain broiler performances under a high stocking density and heat stress conditions through a better redox and immune response. Antioxidants 10, 1542.
Sullivan, L.B., Gui, D.Y., Hosios, A.M., Bush, L.N., Freinkman, E., and Vander Heiden, M.G. (2015). Supporting aspartate biosynthesis is an essential function of respiration in proliferating cells. Cell 162, 552–563.
Sunde, R.A., Li, J.L., and Taylor, R.M. (2016). Insights for setting of nutrient requirements, gleaned by comparison of selenium status biomarkers in turkeys and chickens versus rats, mice, and lambs. Adv Nutr 7, 1129–1138.
Tang, C., Li, S., Zhang, K., Li, J., Han, Y., Zhan, T., Zhao, Q., Guo, X., and Zhang, J. (2020). Selenium deficiency-induced redox imbalance leads to metabolic reprogramming and inflammation in the liver. Redox Biol 36, 101519.
Venardos, K.M., Perkins, A., Headrick, J., and Kaye, D.M. (2007). Myocardial ischemia-reperfusion injury, antioxidant enzyme systems, and selenium: a review. Curr Med Chem 14, 1539–1549.
Wang, X., Wang, S., He, S.L., Zhang, F., Tan, W.H., Lei, Y.X., Yu, H.J., Li, Z., Ning, Y.J., Xiang, Y.Z., et al. (2013). Comparing gene expression profiles of Kashin-Beck and Keshan diseases occurring within the same endemic areas of China. Sci China Life Sci 56, 797–803.
Wang, S.J., Chen, Q., Liu, M.Y., Yu, H.Y., Xu, J.Q., Wu, J.Q., Zhang, Y., and Wang, T. (2019). Regulation effects of rosemary (Rosmarinus officinalis Linn.) on hepatic lipid metabolism in OA induced NAFLD rats. Food Funct 10, 7356–7365.
Welford, R.W.D., Vercauteren, M., Trébaul, A., Cattaneo, C., Eckert, D., Garzotti, M., Sieber, P., Segrestaa, J., Studer, R., Groenen, P.M.A., et al. (2016). Serotonin biosynthesis as a predictive marker of serotonin pharmacodynamics and disease-induced dysregulation. Sci Rep 6, 30059.
Whitacre, M.E., CombsJr., G.F., Combs, S.B., and Parker, R.S. (1987). Influence of dietary vitamin E on nutritional pancreatic atrophy in selenium-deficient chicks. J Nutr 117, 460–467.
Williams, A.M., Ladva, C.N., Leon, J.S., Lopman, B.A., Tangpricha, V., WhiteheadJr, R.D., Armitage, A.E., Wray, K., Morovat, A., Pasricha, S. R., et al. (2019). Changes in micronutrient and inflammation serum biomarker concentrations after a norovirus human challenge. Am J Clin Nutr 110, 1456–1464.
Wu, J., Weisshaar, N., Hotz-Wagenblatt, A., Madi, A., Ma, S., Mieg, A., Hering, M., Mohr, K., Schlimbach, T., Borgers, H., et al. (2020). Skeletal muscle antagonizes antiviral CD8+ T cell exhaustion. Sci Adv 6, eaba3458.
Xing, Y., Liu, Z., Yang, G., Gao, D., and Niu, X. (2015). MicroRNA expression profiles in rats with selenium deficiency and the possible role of the Wnt/β-catenin signaling pathway in cardiac dysfunction. Int J Mol Med 35, 143–152.
Xu, J., Wang, L., Tang, J., Jia, G., Liu, G., Chen, X., Cai, J., Shang, H., and Zhao, H. (2017). Pancreatic atrophy caused by dietary selenium deficiency induces hypoinsulinemic hyperglycemia via global down-regulation of selenoprotein encoding genes in broilers. PLoS ONE 12, e0182079.
Yang, T., Cao, C., Yang, J., Liu, T., Lei, X.G., Zhang, Z., and Xu, S. (2018). miR-200a-5p regulates myocardial necroptosis induced by Se deficiency via targeting RNF11. Redox Biol 15, 159–169.
Yao, L., Du, Q., Yao, H., Chen, X., Zhang, Z., and Xu, S. (2015). Roles of oxidative stress and endoplasmic reticulum stress in selenium deficiency-induced apoptosis in chicken liver. BioMetals 28, 255–265.
Zhang, Y., Zhang, H., and Zhao, B. (2018). Hippo signaling in the immune system. Trends Biochem Sci 43, 77–80.
Zhang, Y., Yu, D., Zhang, J., Bao, J., Tang, C., and Zhang, Z. (2020b). The role of necroptosis and apoptosis through the oxidative stress pathway in the liver of selenium-deficient swine. Metallomics 12, 607–616.
Zhang, Y., Sun, Y., Wu, Z., Xiong, X., Zhang, J., Ma, J., Xiao, S., Huang, L., and Yang, B. (2021). Subcutaneous and intramuscular fat transcriptomes show large differences in network organization and associations with adipose traits in pigs. Sci China Life Sci 64, 1732–1746.
Zhang, Z., Liu, Q., Yang, J., Yao, H., Fan, R., Cao, C., Liu, C., Zhang, S., Lei, X., and Xu, S. (2020a). The proteomic profiling of multiple tissue damage in chickens for a selenium deficiency biomarker discovery. Food Funct 11, 1312–1321.
Zhao, L., Feng, Y., Deng, J., Zhang, N.Y., Zhang, W.P., Liu, X.L., Rajput, S.A., Qi, D.S., and Sun, L.H. (2019). Selenium deficiency aggravates aflatoxin B1-induced immunotoxicity in chick spleen by regulating 6 selenoprotein genes and redox/inflammation/apoptotic signaling. J Nutr 149, 894–901.
Zhao, L., Feng, Y., Xu, Z.J., Zhang, N.Y., Zhang, W.P., Zuo, G., Khalil, M. M., and Sun, L.H. (2021). Selenium mitigated aflatoxin B1-induced cardiotoxicity with potential regulation of 4 selenoproteins and ferroptosis signaling in chicks. Food Chem Toxicol 154, 112320.
Zheng, S., Zhao, J., Xing, H., and Xu, S. (2019). Oxidative stress, inflammation, and glycometabolism disorder-induced erythrocyte hemolysis in selenium-deficient exudative diathesis broilers. J Cell Physiol 234, 16328–16337.
Zhu, Y., Zhou, Z., Huang, T., Zhang, Z., Li, W., Ling, Z., Jiang, T., Yang, J., Yang, S., Xiao, Y., et al. (2022). Mapping and analysis of a spatiotemporal H3K27ac and gene expression spectrum in pigs. Sci China Life Sci 65, 1517–1534.
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This work was supported by the National Natural Science Foundation of China (32102588), the Top-notch Young Talent Supporting Program to LHS and Beijing Deyuanshun Biological Technology Co., Ltd.
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Zhao, L., Liu, M., Sun, H. et al. Selenium deficiency-induced multiple tissue damage with dysregulation of immune and redox homeostasis in broiler chicks under heat stress. Sci. China Life Sci. 66, 2056–2069 (2023). https://doi.org/10.1007/s11427-022-2226-1
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DOI: https://doi.org/10.1007/s11427-022-2226-1