@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 = "Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (MEST) (2018R1A2A1A05077608), Korea Mouse Phenotyping Project (2014M3A9D5A01073556), the Intelligent Synthetic Biology Center of Global Frontier Project (2011-0031955), and the Global Ph.D. Fellowship program (NRF-2015H1A2A1033124) through the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT and future Planning and by intramural research funds of the National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. W.M.C. H.H.K. M.H.K. H.S.Y. Y.S.L. S.Y.K. J.H.L. Y.R.S. K.Y. T.R. and W.I.J. contributed to the design and performance of animal experiments and analysis of data. W.M.C. H.H.K. and Y.E.K. constructed the AAV2/8-Slc7a11-shRNA viral construction. W.M.C. H.S.E. S.H.K. J.H.L. and W.K. contributed to the isolation of human hepatic cells from patients and analyzed the data. Y.J.C. and S.K.K. performed and analyzed sulfur-containing metabolite measurements. J.H.H. C.H.L. and H.S.C. contributed to the generation of chimeric mice. R.C. and W.S. performed measurements of endocannabinoids. B.G. G.K. and W.I.J. wrote the manuscript and provided important advice for experiments. The authors declare no competing interests. Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government ( MEST ) ( 2018R1A2A1A05077608 ), Korea Mouse Phenotyping Project ( 2014M3A9D5A01073556 ), the Intelligent Synthetic Biology Center of Global Frontier Project ( 2011-0031955 ), and the Global Ph.D. Fellowship program (NRF- 2015H1A2A1033124 ) through the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT and future Planning and by intramural research funds of the National Institute on Alcohol Abuse and Alcoholism , Bethesda, MD, USA. 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",
issn = "1550-4131",
publisher = "Cell Press",
number = "5",
}