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Butyrate stimulates hepatic gluconeogenesis in mouse primary hepatocytes

  • Authors:
    • Xueying Ji
    • Feiye Zhou
    • Yuqing Zhang
    • Ruyuan Deng
    • Wan Xu
    • Mengyao Bai
    • Yun Liu
    • Li Shao
    • Xiao Wang
    • Libin Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China, The Very Important Person Department, East Hospital, Shanghai Tongji University School of Medicine, Shanghai 200120, P.R. China
    Copyright: © Ji et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1677-1687
    |
    Published online on: December 28, 2018
       https://doi.org/10.3892/etm.2018.7136
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Abstract

Butyrate is a major short-chain fatty acid (SCFA) produced by microbial fermentation of dietary fiber in the gastrointestinal tract. Butyrate is also a well‑known broad‑spectrum histone deacetylase (HDAC) inhibitor. Butyrate has been reported to improve energy metabolism in rodents, which is associated with its beneficial effects on skeletal muscle, brown fat tissue and pancreatic β‑cells. The present study investigated the direct effect of butyrate on hepatic gluconeogenesis in mouse primary hepatocytes and the underlying mechanism. Isolated mouse primary hepatocytes were incubated with sodium butyrate, other HDAC inhibitors and other SCFAs. Hepatic glucose production was measured and gluconeogenic gene expression was detected by polymerase chain reaction analysis. The phosphorylation of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) was assessed by western blot analysis. The results revealed that sodium butyrate dose‑dependently increased hepatic glucose production and gluconeogenic gene expression in isolated mouse primary hepatocytes. Trichostatin A, a potent broad‑spectrum HDAC inhibitor, had the opposite effect. Similar to sodium butyrate, propionate, which is another SCFA, promoted hepatic glucose production and gluconeogenic gene expression in the presence or absence of gluconeogenic substrates, which were further enhanced by cAMP. Furthermore, sodium butyrate also increased the accumulation of intracellular ATP and induced the phosphorylation of CREB in mouse hepatocytes. In conclusion, the present study suggested that butyrate stimulates hepatic gluconeogenesis and induces gluconeogenic gene expression as a substrate and cAMP/CREB signaling activator.
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Copy and paste a formatted citation
Spandidos Publications style
Ji X, Zhou F, Zhang Y, Deng R, Xu W, Bai M, Liu Y, Shao L, Wang X, Zhou L, Zhou L, et al: Butyrate stimulates hepatic gluconeogenesis in mouse primary hepatocytes. Exp Ther Med 17: 1677-1687, 2019.
APA
Ji, X., Zhou, F., Zhang, Y., Deng, R., Xu, W., Bai, M. ... Zhou, L. (2019). Butyrate stimulates hepatic gluconeogenesis in mouse primary hepatocytes. Experimental and Therapeutic Medicine, 17, 1677-1687. https://doi.org/10.3892/etm.2018.7136
MLA
Ji, X., Zhou, F., Zhang, Y., Deng, R., Xu, W., Bai, M., Liu, Y., Shao, L., Wang, X., Zhou, L."Butyrate stimulates hepatic gluconeogenesis in mouse primary hepatocytes". Experimental and Therapeutic Medicine 17.3 (2019): 1677-1687.
Chicago
Ji, X., Zhou, F., Zhang, Y., Deng, R., Xu, W., Bai, M., Liu, Y., Shao, L., Wang, X., Zhou, L."Butyrate stimulates hepatic gluconeogenesis in mouse primary hepatocytes". Experimental and Therapeutic Medicine 17, no. 3 (2019): 1677-1687. https://doi.org/10.3892/etm.2018.7136
Copy and paste a formatted citation
x
Spandidos Publications style
Ji X, Zhou F, Zhang Y, Deng R, Xu W, Bai M, Liu Y, Shao L, Wang X, Zhou L, Zhou L, et al: Butyrate stimulates hepatic gluconeogenesis in mouse primary hepatocytes. Exp Ther Med 17: 1677-1687, 2019.
APA
Ji, X., Zhou, F., Zhang, Y., Deng, R., Xu, W., Bai, M. ... Zhou, L. (2019). Butyrate stimulates hepatic gluconeogenesis in mouse primary hepatocytes. Experimental and Therapeutic Medicine, 17, 1677-1687. https://doi.org/10.3892/etm.2018.7136
MLA
Ji, X., Zhou, F., Zhang, Y., Deng, R., Xu, W., Bai, M., Liu, Y., Shao, L., Wang, X., Zhou, L."Butyrate stimulates hepatic gluconeogenesis in mouse primary hepatocytes". Experimental and Therapeutic Medicine 17.3 (2019): 1677-1687.
Chicago
Ji, X., Zhou, F., Zhang, Y., Deng, R., Xu, W., Bai, M., Liu, Y., Shao, L., Wang, X., Zhou, L."Butyrate stimulates hepatic gluconeogenesis in mouse primary hepatocytes". Experimental and Therapeutic Medicine 17, no. 3 (2019): 1677-1687. https://doi.org/10.3892/etm.2018.7136
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