{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:04:49Z","timestamp":1787501089838,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,9,5]],"date-time":"2021-09-05T00:00:00Z","timestamp":1630800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["U01 AA024733"],"award-info":[{"award-number":["U01 AA024733"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R37 AA020518"],"award-info":[{"award-number":["R37 AA020518"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK102142"],"award-info":[{"award-number":["R01 DK102142"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Recent evidence demonstrates that alcohol activates the mechanistic target of rapamycin (mTOR) and impairs hepatic transcription factor EB (TFEB) reducing autophagy and contributing to alcohol\u2010induced liver injury. Trehalose, a disaccharide, activates TFEB and protects against diet\u2010induced nonalcoholic fatty liver disease in mice. The aim of the present study was to investigate whether trehalose would reverse the impairment of TFEB induced by alcohol and protect against alcohol\u2010induced liver injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male C57BL\/6J mice were subjected to chronic\u2010plus\u2010binge (Gao\u2010binge) alcohol feeding with and without trehalose supplementation. Some mice were also administrered Alda\u20101, an aldehyde dehydrogenase 2 agonist.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that Alda\u20101 did not affect Gao\u2010binge alcohol\u2010induced mTOR activation and impaired TFEB in mouse livers. Trehalose increased TFEB nuclear translocation, elevated levels of LC3\u2010II and lysosomal proteins in mouse livers and cultured AML12 cells, confirming the activation of TFEB by trehalose. However, trehalose did not improve the impairment in TFEB induced by Gao\u2010binge alcohol. Both Alda\u20101 and trehalose failed to protect against Gao\u2010binge alcohol\u2010induced steatosis and liver injury, based on the serum levels of alanine aminotransferase (ALT), histological analysis, and levels of hepatic triglyceride. Interestingly, trehalose increased expression of pro\u2010inflammatory genes in mouse macrophage RAW264.7 cells and slightly increased the infiltration of hepatic neutrophils and inflammatory cytokine gene expression in Gao\u2010binge alcohol\u2010fed mice livers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Trehalose fails to improve the impaired TFEB induced by Gao\u2010binge alcohol and does not protect against alcohol\u2010induced liver injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.14695","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T02:32:15Z","timestamp":1630895535000},"page":"1950-1964","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Trehalose activates hepatic transcription factor EB (TFEB) but fails to ameliorate alcohol\u2010impaired TFEB and liver injury in mice"],"prefix":"10.1111","volume":"45","author":[{"given":"Xiaojuan","family":"Chao","sequence":"first","affiliation":[{"name":"Department of Pharmacology Toxicology and Therapeutics University of Kansas Medical Center Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaogui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Toxicology and Therapeutics University of Kansas Medical Center Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology Fraternal Order of Eagles Diabetes Research Center The Pappajohn Biomedical Institute Carver College of Medicine University of Iowa Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Min","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Toxicology and Therapeutics University of Kansas Medical Center Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3167-5073","authenticated-orcid":false,"given":"Wen\u2010Xing","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Toxicology and Therapeutics University of Kansas Medical Center Kansas City Kansas 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