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However, the effects of short\u2010term ethanol (EtOH) intake on liver retinoids and ALD are still undefined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using high\u2010performance liquid chromatography and high\u2010performance liquid chromatography coupled with tandem mass spectrometry (HPLC, HPLC\u2013MS\/MS), and molecular biology techniques in mice and cultured human hepatocytes, we investigated the temporal EtOH effects on retinoids and ALD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In female and male mice, acute EtOH intake caused hepatic retinol (ROL) and retinyl palmitate (RP) decreases within hours, whereas it did not significantly change the retinoic acid (RA) levels, and those of the RA catabolism metabolite, 4\u2010oxo\u2010RA. After EtOH withdrawal, the liver recovered the ROL and RP levels within 48\u2009h, whereas RA and 4\u2010oxo\u2010RA levels remained almost undetectable by this time point. Compared with control diet\u2010fed mice, hepatic ROL and RP levels remained decreased in the 10\u2010day and 3\u2010week\u2010long EtOH treatments, while retinyl oleate and linoleate increased. Interestingly, some of the RA signaling receptors, <jats:italic>Rar\u03b2<\/jats:italic>, along with <jats:italic>Cyp26a1<\/jats:italic>, revealed dramatic transcript increases during the 10\u2010day\u2010long experiments that attenuated over time (up to 8\u2009weeks), reflecting impaired RA signaling. Our work also showed that primary human hepatocytes serve as a model to better define the role of EtOH in retinoid biology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This work reveals that acute and short\u2010term exposures to EtOH disrupt retinoid homeostasis, identifying key events in the early pathogenesis of ALD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.70011","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T03:39:19Z","timestamp":1741750759000},"page":"754-770","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ethanol causes rapid decreases in the hepatic retinoid levels shaping the early steps of alcohol\u2010associated liver disease"],"prefix":"10.1111","volume":"49","author":[{"given":"Xiao\u2010Han","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Pharmacology Weill Cornell Medicine  New York New York 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