Glutamate Signaling in Hepatic Stellate Cells Drives Alcoholic Steatosis
DC Field | Value | Language |
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dc.contributor.author | Choi, Won-Mook | - |
dc.contributor.author | Kim, Hee-Hoon | - |
dc.contributor.author | Kim, Myung-Ho | - |
dc.contributor.author | Cinar, Resat | - |
dc.contributor.author | Yi, Hyon-Seung | - |
dc.contributor.author | Eun, Hyuk Soo | - |
dc.contributor.author | Kim, Seok-Hwan | - |
dc.contributor.author | Choi, Young Jae | - |
dc.contributor.author | Lee, Young-Sun | - |
dc.contributor.author | Kim, So Yeon | - |
dc.contributor.author | Seo, Wonhyo | - |
dc.contributor.author | Lee, Jun-Hee | - |
dc.contributor.author | Shim, Young-Ri | - |
dc.contributor.author | Kim, Ye Eun | - |
dc.contributor.author | Yang, Keungmo | - |
dc.contributor.author | Ryu, Tom | - |
dc.contributor.author | Hwang, Jung Hwan | - |
dc.contributor.author | Lee, Chul-Ho | - |
dc.contributor.author | Choi, Hueng-Sik | - |
dc.contributor.author | Gao, Bin | - |
dc.contributor.author | Kim, Won | - |
dc.contributor.author | Kim, Sang Kyum | - |
dc.contributor.author | Kunos, George | - |
dc.contributor.author | Jeong, Won-Il | - |
dc.date.accessioned | 2021-09-01T00:30:45Z | - |
dc.date.available | 2021-09-01T00:30:45Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2019-11-05 | - |
dc.identifier.issn | 1550-4131 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/61927 | - |
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.language.iso | en | - |
dc.publisher | CELL PRESS | - |
dc.subject | LIVER-DISEASE | - |
dc.subject | SELECTIVE BLOCKADE | - |
dc.subject | ENDOCANNABINOID SYSTEM | - |
dc.subject | PLASMA HOMOCYSTEINE | - |
dc.subject | CHRONIC ETHANOL | - |
dc.subject | CB1 RECEPTORS | - |
dc.subject | EXPRESSION | - |
dc.subject | INJURY | - |
dc.subject | PATHOGENESIS | - |
dc.subject | CONSUMPTION | - |
dc.title | Glutamate Signaling in Hepatic Stellate Cells Drives Alcoholic Steatosis | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Young-Sun | - |
dc.identifier.doi | 10.1016/j.cmet.2019.08.001 | - |
dc.identifier.scopusid | 2-s2.0-85074145373 | - |
dc.identifier.wosid | 000495017800007 | - |
dc.identifier.bibliographicCitation | CELL METABOLISM, v.30, no.5, pp.877 - + | - |
dc.relation.isPartOf | CELL METABOLISM | - |
dc.citation.title | CELL METABOLISM | - |
dc.citation.volume | 30 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 877 | - |
dc.citation.endPage | + | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalResearchArea | Endocrinology & Metabolism | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Endocrinology & Metabolism | - |
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 | - |
dc.subject.keywordAuthor | 2-arachidonoylglycerol | - |
dc.subject.keywordAuthor | alcoholic liver disease | - |
dc.subject.keywordAuthor | cannabinoid receptor | - |
dc.subject.keywordAuthor | metabotrophic glutamate receptor 5 | - |
dc.subject.keywordAuthor | Nrf2 | - |
dc.subject.keywordAuthor | transsulfuration pathway | - |
dc.subject.keywordAuthor | xCT | - |
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