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 Gao; Won Kim; Sang Kyum Kim; George Kunos; Won Il Jeong

doi:10.1016/j.cmet.2019.08.001

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 Gao

Won Kim, Sang Kyum Kim, George Kunos, Won Il Jeong

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

86 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 language	English
Pages (from-to)	877-889.e7
Journal	Cell Metabolism
Volume	30
Issue number	5
DOIs	https://doi.org/10.1016/j.cmet.2019.08.001
State	Published - 5 Nov 2019

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

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

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10.1016/j.cmet.2019.08.001

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

@article{ba25bba59cec48eaa8e65a758603dc7f,

title = "Glutamate Signaling in Hepatic Stellate Cells Drives Alcoholic Steatosis",

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.",

keywords = "2-arachidonoylglycerol, Nrf2, alcoholic liver disease, cannabinoid receptor, metabotrophic glutamate receptor 5, transsulfuration pathway, xCT",

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

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = nov,

day = "5",

doi = "10.1016/j.cmet.2019.08.001",

language = "English",

volume = "30",

pages = "877--889.e7",

journal = "Cell Metabolism",

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Choi, WM, Kim, HH, Kim, MH, Cinar, R, Yi, HS, Eun, HS, Kim, SH, Choi, YJ, Lee, YS, Kim, SY, Seo, W, Lee, JH, Shim, YR, Kim, YE, Yang, K, Ryu, T, Hwang, JH, Lee, CH, Choi, HS, Gao, B, Kim, W, Kim, SK, Kunos, G & Jeong, WI 2019, 'Glutamate Signaling in Hepatic Stellate Cells Drives Alcoholic Steatosis', Cell Metabolism, vol. 30, no. 5, pp. 877-889.e7. https://doi.org/10.1016/j.cmet.2019.08.001

TY - JOUR

T1 - Glutamate Signaling in Hepatic Stellate Cells Drives Alcoholic Steatosis

AU - Choi, Won Mook

AU - Kim, Hee Hoon

AU - Kim, Myung Ho

AU - Cinar, Resat

AU - Yi, Hyon Seung

AU - Eun, Hyuk Soo

AU - Kim, Seok Hwan

AU - Choi, Young Jae

AU - Lee, Young Sun

AU - Kim, So Yeon

AU - Seo, Wonhyo

AU - Lee, Jun Hee

AU - Shim, Young Ri

AU - Kim, Ye Eun

AU - Yang, Keungmo

AU - Ryu, Tom

AU - Hwang, Jung Hwan

AU - Lee, Chul Ho

AU - Choi, Hueng Sik

AU - Gao, Bin

AU - Kim, Won

AU - Kim, Sang Kyum

AU - Kunos, George

AU - Jeong, Won Il

PY - 2019/11/5

Y1 - 2019/11/5

N2 - 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.

AB - 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.

KW - 2-arachidonoylglycerol

KW - Nrf2

KW - alcoholic liver disease

KW - cannabinoid receptor

KW - metabotrophic glutamate receptor 5

KW - transsulfuration pathway

KW - xCT

UR - https://www.scopus.com/pages/publications/85074145373

U2 - 10.1016/j.cmet.2019.08.001

DO - 10.1016/j.cmet.2019.08.001

M3 - Article

C2 - 31474565

AN - SCOPUS:85074145373

SN - 1550-4131

VL - 30

SP - 877-889.e7

JO - Cell Metabolism

JF - Cell Metabolism

IS - 5

ER -

Glutamate Signaling in Hepatic Stellate Cells Drives Alcoholic Steatosis

Abstract

Bibliographical note

Keywords

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