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 journalArticlepeer-review

41 Scopus citations

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
StatePublished - 5 Nov 2019

Keywords

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

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