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Decreased NMNAT1 expression and activity were observed in the liver of patients with alcohol-associated hepatitis and either liver or primary hepatocytes from ALD mice. F-box and WD repeat domain containing 7 (FBXW7)\u2013regulated interferon regulatory factor 1 (IRF1) ubiquitination degradation contributed to the alcohol-inhibited NMNAT1 transcriptional level. Hepatic NMNAT1 knockout aggravated alcohol-induced hepatic NAD\n                    <jats:sup>+<\/jats:sup>\n                    decline and further hepatic steatosis and liver injury. Metabolomics and transcriptomics interaction revealed that the cysteine sulfinic acid decarboxylase (CSAD)\u2013regulated taurine pathway was involved in NMNAT1-disrupted hepatic lipid metabolism in ALD. Hepatic CSAD overexpression or taurine supply attenuated hepatic NMNAT1 knockout\u2013aggravated ALD. Hepatic NMNAT1 loss inhibited NMN-protected ALD. Replenishing hepatic NMNAT1 reversed liver lipid accumulation in ALD mice. These findings identified NMNAT1 as a promising therapeutic target for ALD.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adt6195","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T21:26:20Z","timestamp":1753478780000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":11,"title":["Hepatic NMNAT1 is required to defend against alcohol-associated fatty liver disease"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8664-5368","authenticated-orcid":true,"given":"Qinchao","family":"Ding","sequence":"first","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, PR. 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