{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:12:17Z","timestamp":1791951137276,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcohol, Clinical and Experimental Research"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acetaldehyde (AcH), a highly reactive metabolite of ethanol, plays a pivotal role in the pathogenesis of alcohol\u2010associated liver disease (ALD) and alcohol use disorder (AUD). Post alcohol consumption, AcH generated in hepatocytes is further metabolized into acetate by aldehyde dehydrogenase 2 (ALDH2) or excreted into circulation and bile via the basolateral and apical membranes, respectively. Our previous studies have demonstrated that aquaporin 8 (AQP8), which is a water channel and mainly expressed on the apical membrane, facilitates AcH excretion into bile. AQP9 is predominantly expressed on the basolateral membrane of hepatocytes; however, the roles of AQP9 in AcH relocation and pathogenesis of ALD and AUD remain unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      AQP9 expression was examined in human ALD liver samples. The role of AQP9 was investigated by using the NIAAA mouse model of ALD, voluntary and binge\u2010drinking behavior paradigms, global\n                      <jats:italic>Aqp9<\/jats:italic>\n                      knockout (KO) mice, in\u00a0situ liver perfusion, and primary hepatocyte culture\u00a0assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our data demonstrated that hepatic AQP9 expression was markedly downregulated in ALD patients and correlated with liver injury markers and metabolic gene expression. In mice,\n                      <jats:italic>Aqp9<\/jats:italic>\n                      KO ameliorated early\u2010stage ALD by reducing hepatic lipogenesis, lipid peroxidation, and inflammation. In\u00a0vivo and in\u00a0vitro experiments revealed that AQP9 promotes AcH influx into hepatocytes. By using drinking in the dark experiments, we found that\n                      <jats:italic>Aqp9<\/jats:italic>\n                      KO mice had reduced binge\u2010like alcohol consumption compared with wild\u2010type mice, while two\u2010bottle choice experiments revealed that\n                      <jats:italic>Aqp9<\/jats:italic>\n                      KO mice had slightly higher alcohol preference compared with wild\u2010type mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggest that AQP9 promotes hepatocytes to take up AcH, thereby exacerbating ALD progression and regulating alcohol\u2010drinking behavior.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.70272","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T15:00:25Z","timestamp":1775487625000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Aquaporin 9 regulates acetaldehyde uptake, alcohol\u2010induced liver injury, and drinking behavior"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8024-5128","authenticated-orcid":false,"given":"Cheng","family":"Chen","sequence":"first","affiliation":[{"name":"Laboratory of Liver Diseases National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"},{"name":"Laboratory of Physiologic Studies National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9840-2013","authenticated-orcid":false,"given":"Bryan","family":"Mackowiak","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dechun","family":"Feng","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukun","family":"Guan","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010hong","family":"Lin","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaojie","family":"Fu","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoupeng","family":"Wei","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative Neuroscience National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory for Integrative Neuroscience National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Kunos","sequence":"additional","affiliation":[{"name":"Laboratory of Physiologic Studies National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Gao","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.06.035"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1039\/tf9524800439"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.032"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0437994100"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2012.08.002"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-017-0327-y"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.02.042"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30866"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.03.021"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3505"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/egastro-2025-100189"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000890"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-024-01063-2"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/egastro-2024-100104"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.04.012"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI178616"},{"issue":"25","key":"e_1_2_9_18_1","first-page":"974","article-title":"Targeting liver aldehyde dehydrogenase\u20102 prevents heavy but not moderate alcohol drinking","volume":"116","author":"Guillot A.","year":"2019","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-015-1788-6"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-021-00357-z"},{"key":"e_1_2_9_21_1","first-page":"66","article-title":"Acetaldehyde dehydrogenases in liver zonation and liver cancer","volume":"22","author":"Jin\u2010Smith B.","year":"2023","journal-title":"Gene Expression"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1469"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/002689797172507"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agad077"},{"issue":"100","key":"e_1_2_9_25_1","first-page":"29","article-title":"Deciphering the cell type\u2010specific and zonal distribution of drug\u2010metabolizing enzymes, transporters, and transcription factors in livers of mice using single\u2010cell transcriptomics","volume":"53","author":"Lim J.J.","year":"2025","journal-title":"Drug Metabolism and Disposition"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.70126"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-023-00734-9"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI157780"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI176345"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20996"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mpaic.2011.11.005"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1177\/002215540104901208"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-7364-3-2-121"},{"key":"e_1_2_9_34_1","first-page":"258","article-title":"Role of acetaldehyde in mediating the pharmacological and behavioral effects of alcohol","volume":"29","author":"Quertemont E.","year":"2006","journal-title":"Alcohol Research & Health"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2003.07.001"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2013.234"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610894104"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-022-00257-7"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.06.018"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2013.08.005"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2003.tb04396.x"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.01.153"},{"issue":"102","key":"e_1_2_9_43_1","first-page":"246","article-title":"Aquaporin\u20109 facilitates liver regeneration following hepatectomy","volume":"50","author":"Zhang B.","year":"2022","journal-title":"Redox Biology"}],"container-title":["Alcohol, Clinical and Experimental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.70272","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acer.70272","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.70272","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:13:01Z","timestamp":1779084781000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acer.70272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":42,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/acer.70272"],"URL":"https:\/\/doi.org\/10.1111\/acer.70272","archive":["Portico"],"relation":{},"ISSN":["2993-7175","2993-7175"],"issn-type":[{"value":"2993-7175","type":"print"},{"value":"2993-7175","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-09-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70272"}}