{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:46:28Z","timestamp":1791276388163,"version":"4.1.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":118,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p>Carbohydrate responsive element binding protein (ChREBP) is central for <jats:italic toggle=\"yes\">de novo<\/jats:italic> fatty acid synthesis under physiological conditions and in the context of nonalcoholic fatty liver disease. We explored its contribution to alcohol\u2010induced steatosis in a mouse model of binge drinking as acute ethanol (EtOH) intoxication has become an alarming health problem. Within 6 hours, ChREBP acetylation and its recruitment onto target gene promoters were increased in liver of EtOH\u2010fed mice. Acetylation of ChREBP was dependent on alcohol metabolism because inhibition of alcohol dehydrogenase (ADH) activity blunted ChREBP EtOH\u2010induced acetylation in mouse hepatocytes. Transfection of an acetylation\u2010defective mutant of ChREBP (ChREBP<jats:sup>K672A<\/jats:sup>) in HepG2 cells impaired the stimulatory effect of EtOH on ChREBP activity. Importantly, ChREBP silencing in the liver of EtOH\u2010fed mice prevented alcohol\u2010induced triglyceride accumulation through an inhibition of the lipogenic pathway but also led, unexpectedly, to hypothermia, increased blood acetaldehyde concentrations, and enhanced lethality. This phenotype was associated with impaired hepatic EtOH metabolism as a consequence of reduced ADH activity. While the expression and activity of the NAD<jats:sup>+<\/jats:sup> dependent deacetylase sirtuin 1, a ChREBP\u2010negative target, were down\u2010regulated in the liver of alcohol\u2010fed mice, they were restored to control levels upon ChREBP silencing. In turn, ADH acetylation was reduced, suggesting that ChREBP regulates EtOH metabolism and ADH activity through its direct control of sirtuin 1 expression. Indeed, when sirtuin 1 activity was rescued by resveratrol pretreatment in EtOH\u2010treated hepatocytes, a significant decrease in ADH protein content and\/or acetylation was observed. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: our study describes a novel role for ChREBP in EtOH metabolism and unravels its protective effect against severe intoxication in response to binge drinking. (H<jats:sc>epatology<\/jats:sc> 2015;62:1086\u20101100)<\/jats:p>","DOI":"10.1002\/hep.27778","type":"journal-article","created":{"date-parts":[[2015,3,11]],"date-time":"2015-03-11T23:35:32Z","timestamp":1426116932000},"page":"1086-1100","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":68,"title":["Novel role for carbohydrate responsive element binding protein in the control of ethanol metabolism and susceptibility to binge drinking"],"prefix":"10.1097","volume":"62","author":[{"given":"Solenne","family":"Marmier","sequence":"first","affiliation":[{"name":"Inserm U1016 Institut Cochin,Paris,France"},{"name":"CNRS UMR 8104,Paris,France"},{"name":"Universit\u00e9 Paris Descartes,Sorbonne Paris Cit\u00e9, Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"Dentin","sequence":"additional","affiliation":[{"name":"Inserm U1016 Institut Cochin,Paris,France"},{"name":"CNRS UMR 8104,Paris,France"},{"name":"Universit\u00e9 Paris Descartes,Sorbonne Paris Cit\u00e9, Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Daujat\u2010Chavanieu","sequence":"additional","affiliation":[{"name":"INSERM, U1040, Institut de Recherche en Bioth\u00e9rapie,Montpellier,France"},{"name":"Universit\u00e9 Montpellier 1, UMR 1040,Montpellier,France"},{"name":"CHU Montpellier,Institut de Recherche en Bioth\u00e9rapie,Montpellier,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Guillou","sequence":"additional","affiliation":[{"name":"INRA\u2010ToxAlim,Toxicologie Int\u00e9grative et M\u00e9tabolisme,Toulouse,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Bertrand\u2010Michel","sequence":"additional","affiliation":[{"name":"Plateau de lipidomique IFR\u2010BMT,INSERM,Plateforme MetaToul,Toulouse,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Gerbal\u2010Chaloin","sequence":"additional","affiliation":[{"name":"INSERM, U1040, Institut de Recherche en Bioth\u00e9rapie,Montpellier,France"},{"name":"Universit\u00e9 Montpellier 1, UMR 1040,Montpellier,France"},{"name":"CHU Montpellier,Institut de Recherche en Bioth\u00e9rapie,Montpellier,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Girard","sequence":"additional","affiliation":[{"name":"Inserm U1016 Institut Cochin,Paris,France"},{"name":"CNRS UMR 8104,Paris,France"},{"name":"Universit\u00e9 Paris Descartes,Sorbonne Paris Cit\u00e9, Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Lotersztajn","sequence":"additional","affiliation":[{"name":"Inserm UMR 1149\u2010Center for Research on Inflammation,Paris,France"},{"name":"Universit\u00e9 Paris Diderot,Sorbonne Paris Cit\u00e9, Facult\u00e9 de M\u00e9decine Xavier Bichat,Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Postic","sequence":"additional","affiliation":[{"name":"Inserm U1016 Institut Cochin,Paris,France"},{"name":"CNRS UMR 8104,Paris,France"},{"name":"Universit\u00e9 Paris Descartes,Sorbonne Paris Cit\u00e9, Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2015,5,6]]},"reference":[{"key":"hep27778-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1053\/j.gastro.2011.09.002","article-title":"Alcoholic liver disease: pathogenesis and new therapeutic targets","volume":"141","year":"2011","journal-title":"Gastroenterology"},{"key":"hep27778-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"178","DOI":"10.4161\/oxim.3.3.12288","article-title":"Acetaldehyde adducts in alcoholic liver disease","volume":"3","year":"2010","journal-title":"Oxid Med 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