DC Field | Value | Language |
---|---|---|
dc.contributor.author | Choi, Won-Mook | ko |
dc.contributor.author | Kim, Hee-Hoon | ko |
dc.contributor.author | Kim, Myung-Ho | ko |
dc.contributor.author | Cinar, Resat | ko |
dc.contributor.author | Yi, Hyon-Seung | ko |
dc.contributor.author | Eun, Hyuk Soo | ko |
dc.contributor.author | Kim, Seok-Hwan | ko |
dc.contributor.author | Choi, Young Jae | ko |
dc.contributor.author | Lee, Young-Sun | ko |
dc.contributor.author | Kim, So Yeon | ko |
dc.contributor.author | Seo, Wonhyo | ko |
dc.contributor.author | Lee, Jun-Hee | ko |
dc.contributor.author | Shim, Young-Ri | ko |
dc.contributor.author | Kim, Ye Eun | ko |
dc.contributor.author | Yang, Keungmo | ko |
dc.contributor.author | Ryu, Tom | ko |
dc.contributor.author | Hwang, Jung Hwan | ko |
dc.contributor.author | Lee, Chul-Ho | ko |
dc.contributor.author | Choi, Hueng-Sik | ko |
dc.contributor.author | Gao, Bin | ko |
dc.contributor.author | Kim, Won | ko |
dc.contributor.author | Kim, Sang Kyum | ko |
dc.contributor.author | Kunos, George | ko |
dc.contributor.author | Jeong, Won-Il | ko |
dc.date.accessioned | 2019-12-13T07:21:02Z | - |
dc.date.available | 2019-12-13T07:21:02Z | - |
dc.date.created | 2019-12-02 | - |
dc.date.created | 2019-12-02 | - |
dc.date.created | 2019-12-02 | - |
dc.date.created | 2019-12-02 | - |
dc.date.issued | 2019-11 | - |
dc.identifier.citation | CELL METABOLISM, v.30, no.5, pp.877 - 889 | - |
dc.identifier.issn | 1550-4131 | - |
dc.identifier.uri | http://hdl.handle.net/10203/268851 | - |
dc.description.abstract | Activation of hepatocyte cannabinoid receptor-1 (CB1R) by hepatic stellate cell (HSC)-derived 2-arachidonoylglycerol (2-AG) drives de novo lipogenesis in alcoholic liver disease (ALD). How alcohol stimulates 2-AG production in HSCs is unknown. Here, we report that chronic alcohol consumption induced hepatic cysteine deficiency and subsequent glutathione depletion by impaired transsulfuration pathway. A compensatory increase in hepatic cystine-glutamate anti-porter xCT boosted extracellular glutamate levels coupled to cystine uptake both in mice and in patients with ALD. Alcohol also induced the selective expression of metabotropic glutamate receptor-5 (mGluR5) in HSCs where mGluR5 activation stimulated 2-AG production. Consistently, genetic or pharmacologic inhibition of mGluR5 or xCT attenuated alcoholic steatosis in mice via the suppression of 2-AG production and subsequent CB1R-mediated de novo lipogenesis. We conclude that a bidirectional signaling operates at a metabolic synapse between hepatocytes and HSCs through xCT-mediated glutamate-mGluR5 signaling to produce 2-AG, which induces CB1R-mediated alcoholic steatosis. | - |
dc.language | English | - |
dc.publisher | CELL PRESS | - |
dc.title | Glutamate Signaling in Hepatic Stellate Cells Drives Alcoholic Steatosis | - |
dc.type | Article | - |
dc.identifier.wosid | 000495017800007 | - |
dc.identifier.scopusid | 2-s2.0-85074145373 | - |
dc.type.rims | ART | - |
dc.citation.volume | 30 | - |
dc.citation.issue | 5 | - |
dc.citation.beginningpage | 877 | - |
dc.citation.endingpage | 889 | - |
dc.citation.publicationname | CELL METABOLISM | - |
dc.identifier.doi | 10.1016/j.cmet.2019.08.001 | - |
dc.contributor.localauthor | Jeong, Won-Il | - |
dc.contributor.nonIdAuthor | Cinar, Resat | - |
dc.contributor.nonIdAuthor | Kim, Seok-Hwan | - |
dc.contributor.nonIdAuthor | Choi, Young Jae | - |
dc.contributor.nonIdAuthor | Hwang, Jung Hwan | - |
dc.contributor.nonIdAuthor | Lee, Chul-Ho | - |
dc.contributor.nonIdAuthor | Choi, Hueng-Sik | - |
dc.contributor.nonIdAuthor | Gao, Bin | - |
dc.contributor.nonIdAuthor | Kim, Won | - |
dc.contributor.nonIdAuthor | Kim, Sang Kyum | - |
dc.contributor.nonIdAuthor | Kunos, George | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | LIVER-DISEASE | - |
dc.subject.keywordPlus | SELECTIVE BLOCKADE | - |
dc.subject.keywordPlus | ENDOCANNABINOID SYSTEM | - |
dc.subject.keywordPlus | PLASMA HOMOCYSTEINE | - |
dc.subject.keywordPlus | CHRONIC ETHANOL | - |
dc.subject.keywordPlus | CB1 RECEPTORS | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | INJURY | - |
dc.subject.keywordPlus | PATHOGENESIS | - |
dc.subject.keywordPlus | CONSUMPTION | - |
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