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Increased Expression of PHGDH Under High-Selenium Stress In Vivo

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Abstract

The purpose of this study is to explore the glycolytic remodeling under high-selenium (Se) stress. Three groups of male C57BL/6J mice were fed on diets with different Se contents (0.03, 0.15, and 0.30 mg Se/kg). Glucose tolerance test (GTT) and insulin tolerance test (ITT) were measured at the third month. Mice were killed at the fourth month. Plasma, liver, and muscle tissues were fetched for biochemistry and Se analysis. The expressions of insulin signaling pathway (PI3K-AKT-mTOR), glutathione peroxidase 1 (GPX1), selenoprotein N (SELENON), 3-phosphoglycerate dehydrogenase (PHGDH), serine hydroxymethyltransferases 1 (SHMT1), 5,10-methylenetetrahydrofolate reductase (MTHFR), and methionine synthase (MS) were analyzed by western blotting (WB) in liver and muscle tissues. The results of GTT and ITT showed that glucose tolerance and insulin tolerance were both abnormal in the 0.03 mg Se/kg and 0.3 mg Se/kg groups. Se concentrations in plasma, liver, and muscle of 0.03 mg Se/kg group were significantly lower than that of 0.15 mg Se/kg and 0.30 mg Se/kg groups (p < 0.05 or p < 0.01). The expressions of P-Akt (Thr-308) in muscle (p < 0.05) and PI3K and mTOR in liver (p < 0.001) of 0.30 mg Se/kg group were downregulated. The expressions of GPX1 in liver and muscle (p < 0.05 and p < 0.001), SELENON in muscle (p < 0.05), PHGDH in liver and muscle (p < 0.05), and SHMT1 (p < 0.05), MTHFR (p < 0.001), and MS (p < 0.001) in muscle of 0.3 mg Se/kg group were upregulated. The de novo serine synthesis pathway (SSP) was found to be activated in liver and muscle tissues of mice with a high-Se diet for the first time.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China under Grant No. 81973048.

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Authors and Affiliations

  1. Department of Nutrition and Metabolism, Chinese Center for Disease Control and Prevention, National Institute for Nutrition and Health, Beijing, 100050, China

    Qin Wang, Jianrong Wang, Xue Zhang, Yiqun Liu, Feng Han & Xuesong Xiang

  2. College of Resources and Environmental Sciences, China Agricultural University, Beijing, 100193, China

    Yanbin Guo

  3. The Key Laboratory of Trace Element Nutrition, National Health Commission of the People’s Republic of China, Beijing, China

    Zhen-wu Huang

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  1. Qin Wang
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Zhenwu Huang and Qin Wang designed research; Qin Wang, Xue Zhang, and Jianrong Wang conducted laboratory works; Qin Wang, Yiqun Liu, and Feng Han analyzed data; Qin Wang wrote the original manuscript. Xuesong Xiang and Yanbin Guo gave helpful comments. Zhenwu Huang is responsible for the contents of the final manuscript. All authors read and approved the final manuscript.

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Wang, Q., Wang, J., Zhang, X. et al. Increased Expression of PHGDH Under High-Selenium Stress In Vivo. Biol Trace Elem Res (2024). https://doi.org/10.1007/s12011-024-04079-7

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