{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T16:33:18Z","timestamp":1781627598390,"version":"3.54.5"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,3,16]],"date-time":"2015-03-16T00:00:00Z","timestamp":1426464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Core Research for Evolutional Science and Technology from the JST"},{"name":"JSPS KAKENHI","award":["24390075"],"award-info":[{"award-number":["24390075"]}]},{"name":"MEXT KAKENHI","award":["23116002"],"award-info":[{"award-number":["23116002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:p>Nutritional steatohepatitis is closely associated with dysregulation of lipid metabolism and oxidative stress control. <jats:styled-content style=\"fixed-case\">ADH<\/jats:styled-content>3 is a highly conserved bifunctional enzyme involved in formaldehyde detoxification and termination of nitric oxide signaling. Formaldehyde and nitric oxide are nonenzymatically conjugated with glutathione, which is regenerated after <jats:styled-content style=\"fixed-case\">ADH<\/jats:styled-content>3 metabolizes the conjugates. To clarify roles of <jats:styled-content style=\"fixed-case\">ADH<\/jats:styled-content>3 in nutritional liver diseases, we placed <jats:italic>Adh3<\/jats:italic>\u2010null mice on a methionine\u2010 and choline\u2010deficient (<jats:styled-content style=\"fixed-case\">MCD<\/jats:styled-content>) diet. The <jats:italic>Adh3<\/jats:italic>\u2010null mice developed steatohepatitis more rapidly than wild\u2010type mice, indicating that <jats:styled-content style=\"fixed-case\">ADH<\/jats:styled-content>3 protects liver from nutritional steatohepatitis. <jats:styled-content style=\"fixed-case\">NRF<\/jats:styled-content>2, which is a key regulator of cytoprotective genes against oxidative stress, was activated in the <jats:italic>Adh3<\/jats:italic>\u2010null mice with liver damage. In the absence of <jats:styled-content style=\"fixed-case\">NRF<\/jats:styled-content>2, the <jats:italic>Adh3<\/jats:italic> disruption caused severe steatohepatitis by the <jats:styled-content style=\"fixed-case\">MCD<\/jats:styled-content> diet feeding accompanied by significant decrease in glutathione, suggesting cooperative function between <jats:styled-content style=\"fixed-case\">ADH<\/jats:styled-content>3 and <jats:styled-content style=\"fixed-case\">NRF<\/jats:styled-content>2 in the maintenance of cellular glutathione level for cytoprotection. Conversely, with enhanced <jats:styled-content style=\"fixed-case\">NRF<\/jats:styled-content>2 activity, the <jats:italic>Adh3<\/jats:italic> disruption did not cause steatohepatitis but induced steatosis, suggesting that perturbation of lipid metabolism in <jats:styled-content style=\"fixed-case\">ADH<\/jats:styled-content>3\u2010deficiency is not compensated by <jats:styled-content style=\"fixed-case\">NRF<\/jats:styled-content>2. Thus, <jats:styled-content style=\"fixed-case\">ADH<\/jats:styled-content>3 protects liver from steatosis by supporting normal lipid metabolism and prevents progression of steatosis into steatohepatitis by maintaining the cellular glutathione level.<\/jats:p>","DOI":"10.1111\/gtc.12237","type":"journal-article","created":{"date-parts":[[2015,3,16]],"date-time":"2015-03-16T10:23:13Z","timestamp":1426501393000},"page":"464-480","source":"Crossref","is-referenced-by-count":24,"title":["Alcohol dehydrogenase 3 contributes to the protection of liver from nonalcoholic steatohepatitis"],"prefix":"10.1111","volume":"20","author":[{"given":"Maki","family":"Goto","sequence":"first","affiliation":[{"name":"Department of Gene Expression Regulation Institute of Development, Aging and Cancer Tohoku University 4\u20101 Seiryo\u2010machi Aoba\u2010ku Sendai 980\u20108575 Japan"},{"name":"Department of Orthodontics and Dentofacial Orthopedics Graduate School of Dentistry Tohoku University 4\u20101 Seiryo\u2010machi Aoba\u2010ku Sendai 980\u20108575 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kitamura","sequence":"additional","affiliation":[{"name":"Department of Gene Expression Regulation Institute of Development, Aging and Cancer Tohoku University 4\u20101 Seiryo\u2010machi Aoba\u2010ku Sendai 980\u20108575 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Morshedul","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Gene Expression Regulation Institute of Development, Aging and Cancer Tohoku University 4\u20101 Seiryo\u2010machi Aoba\u2010ku Sendai 980\u20108575 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nao","family":"Ota","sequence":"additional","affiliation":[{"name":"Department of Gene Expression Regulation Institute of Development, Aging and Cancer Tohoku University 4\u20101 Seiryo\u2010machi Aoba\u2010ku Sendai 980\u20108575 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Haseba","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine Nippon Medical School 1\u20101\u20105 Sendagi Bunkyo\u2010ku, Tokyo 113\u20100022 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Akimoto","sequence":"additional","affiliation":[{"name":"Division of Laboratory Animal Science Nippon Medical 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