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Lithium Chloride Promotes Milk Protein and Fat Synthesis in Bovine Mammary Epithelial Cells via HIF-1α and β-Catenin Signaling Pathways

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Abstract

Lithium is one of the trace elements with many physiological properties, such as being anti-cancer, anti-viral, and anti-inflammatory. However, little is known about its effect on milk synthesis during lactation. Therefore, we selected different concentrations (5 mM, 10 mM, and 20 mM) of lithium chloride (LiCl) and assessed the effect of LiCl on bovine mammary epithelial (MAC-T) cells that underwent 4 days of differentiation induction. Moreover, we analyzed the effect of LiCl on the expression of genes related to milk fat and milk protein synthesis. Herein, LiCl (5–20 mM) significantly increased the expression of β-casein, promoted mRNA expression and phosphorylated protein expression of the signal transduction molecule and activator of transcription 5β (STAT5-β), and inhibited mRNA and protein expression of suppressor of cytokine signaling 2 (SOCS2). In contrast, 5 and 10 mM LiCl significantly inhibited expression of SOCS3. LiCl at concentration of 5–20 mM enhanced phosphorylation level of mTOR protein; at 10 mM and 20 mM, LiCl significantly promoted expression and phosphorylation of downstream ribosomal protein S6 kinase beta-1 (S6K1) protein. Considering milk fat synthesis, mRNA expression of acetyl CoA carboxylase (ACC) and lipoprotein lipase (LPL) genes was considerably increased in the presence of LiCl (5–20 mM). Additionally, increased protein expression levels of stearoyl-CoA desaturase (SCD), peroxisome proliferator–activated receptor-γ (PPARγ), and sterol regulatory element-binding protein 1 (SREBP1) were observed at all LiCl concentrations tested. Subsequently, LiCl (5–20 mM) significantly promoted protein expression and phosphorylation of β-catenin, while 10 mM and 20 mM of LiCl significantly promoted protein expression of hypoxia-inducible factor-1α (HIF-1α). Collectively, it has been shown that 10 mM LiCl can effectively activate HIF-1α, β-catenin, and β-catenin downstream signaling pathways. Conversely, at 10 mM, LiCl inhibited SOCS2 and SOCS3 protein expression through JAK2/STAT5, mTOR, and SREBP1 signaling pathways, improving synthesis of milk protein and fat. Therefore, LiCl can be used as a potential nutrient to regulate milk synthesis in dairy cows.

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Data are available for consultation upon request to the corresponding author.

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Acknowledgements

We gratefully acknowledge Professor Hong-Gu Lee (Department of Animal Science and Technology, Sanghuh College of Life Sciences, Konkuk University, Seoul 05029, Korea) for generously providing MAC-T cells for cell culture assays.

Funding

This study was funded by the Jilin Provincial Department of Education (grant number JJKH20201022KJ) and the National Natural Science Foundation of China (grant number 31301996).

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Author notes

  1. Zong Jinxin and Shen Jinglin contributed equally to this work.

Authors and Affiliations

  1. Department of Animal Science, College of Animal Science, Jilin University, Changchun, 130062, People’s Republic of China

    Jinxin Zong, Jinglin Shen, Xinlu Liu, Jiayi Liu, Jing Zhang, Changhai Zhou, Yating Fan & Yongcheng Jin

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  1. Jinxin Zong
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  2. Jinglin Shen
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  3. Xinlu Liu
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  4. Jiayi Liu
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  5. Jing Zhang
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  6. Changhai Zhou
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  7. Yating Fan
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  8. Yongcheng Jin
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Contributions

Y. Jin, J. Shen and J. Zhang: conceptualization; J. Zong: methodology; J. Zong, X. Liu and J. Liu: validation; X. Liu, J. Liu and Y. Fan: investigation; J. Shen, J. Zhang and C. Zhou: resources; J. Zong: data curation; J. Zong: writing—original draft preparation; Y. Jin: writing—review and editing; J. Zong: visualization; Y. Jin and J. Shen: supervision; Y. Jin: project administration; Y. Jin: funding acquisition. All authors have read and agreed to the current version of the manuscript.

Corresponding author

Correspondence to Yongcheng Jin.

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This study did not involve any human or animal testing.

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The authors declare no competing interests.

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Zong, J., Shen, J., Liu, X. et al. Lithium Chloride Promotes Milk Protein and Fat Synthesis in Bovine Mammary Epithelial Cells via HIF-1α and β-Catenin Signaling Pathways. Biol Trace Elem Res 201, 180–195 (2023). https://doi.org/10.1007/s12011-022-03131-8

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  • DOI: https://doi.org/10.1007/s12011-022-03131-8

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