Glutamate Signaling in Hepatic Stellate Cells Drives Alcoholic Steatosis

Won Mook Choi, Hee Hoon Kim, Myung Ho Kim, Resat Cinar, Hyon Seung Yi, Hyuk Soo Eun, Seok Hwan Kim, Young Jae Choi, Young Sun Lee, So Yeon Kim, Wonhyo Seo, Jun Hee Lee, Young Ri Shim, Ye Eun Kim, Keungmo Yang, Tom Ryu, Jung Hwan Hwang, Chul Ho Lee, Hueng Sik Choi, Bin GaoWon Kim, Sang Kyum Kim, George Kunos, Won Il Jeong

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Choi et al. show that chronic alcohol consumption induces CYP2E1-mediated reactive oxygen species (ROS) production by hepatocytes, which is compensated by GSH generation through xCT-mediated uptake of cystine. The parallel release of glutamate stimulates mGluR5 on hepatic stellate cells (HSCs) to produce 2-AG, which, in turn, activates CB1R on neighboring hepatocytes to induce de novo lipogenesis.

Original languageEnglish
Pages (from-to)877-889.e7
JournalCell Metabolism
Volume30
Issue number5
DOIs
Publication statusPublished - 2019 Nov 5

Keywords

  • 2-arachidonoylglycerol
  • Nrf2
  • alcoholic liver disease
  • cannabinoid receptor
  • metabotrophic glutamate receptor 5
  • transsulfuration pathway
  • xCT

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Choi, W. M., Kim, H. H., Kim, M. H., Cinar, R., Yi, H. S., Eun, H. S., Kim, S. H., Choi, Y. J., Lee, Y. S., Kim, S. Y., Seo, W., Lee, J. H., Shim, Y. R., Kim, Y. E., Yang, K., Ryu, T., Hwang, J. H., Lee, C. H., Choi, H. S., ... Jeong, W. I. (2019). Glutamate Signaling in Hepatic Stellate Cells Drives Alcoholic Steatosis. Cell Metabolism, 30(5), 877-889.e7. https://doi.org/10.1016/j.cmet.2019.08.001