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Moreover, little is known about whether and how nonethanol ingredients in alcoholic beverages regulate the pathogenesis of ALD. Here the discovery of a small molecule that activates the production and secretion of fibroblast growth factor 21 (FGF21) is reported. It is shown that the activator ethyl lactate, a nonethanol ingredient found in distilled liquors, ameliorates alcoholic hepatosteatosis, inflammation and acute\u2010on\u2010chronic liver injury by stimulating FGF21. In response to chronic\u2010plus\u2010binge ethanol feeding or fasting, ethyl lactate mimics lipogenesis lowering effects by stimulating FGF21 production through the NAD\n                    <jats:sup>+<\/jats:sup>\n                    \u2010dependent deacetylase sirtuin 1 (SIRT1) signaling pathway. These ethyl lactate\u2010mediated beneficial effects are abolished by inhibition of SIRT1 through injection of EX527. Importantly, FGF21 deficiency in hepatocytes blocks the downregulation of lipogenesis by ethyl lactate and exacerbates alcoholic steatosis, inflammation and liver injury. The regulatory mechanism is discussed during the pathophysiological conditions and suggests new lines of research into the therapeutic use of a foodborne small molecule ethyl lactate.\n                  <\/jats:p>","DOI":"10.1002\/advs.202409516","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T14:29:19Z","timestamp":1733927359000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Ethyl Lactate Ameliorates Hepatic Steatosis and Acute\u2010on\u2010Chronic Liver Injury in Alcohol\u2010Associated Liver Disease by Inducing Fibroblast Growth Factor 21"],"prefix":"10.1002","volume":"12","author":[{"given":"Yang","family":"Jiang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety College of Biotechnology Tianjin University of Science and Technology  Tianjin 300457 China"},{"name":"CAS Key Laboratory of Nutrition Metabolism and Food Safety Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences  Shanghai 200031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Wei","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition Metabolism and Food Safety Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences  Shanghai 200031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiming","family":"Shen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety College of Biotechnology Tianjin University of Science and Technology  Tianjin 300457 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiao","family":"Liu","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition Metabolism and Food Safety Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences  Shanghai 200031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weitong","family":"Su","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition Metabolism and Food Safety Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences  Shanghai 200031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Ding","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition Metabolism and Food Safety Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences  Shanghai 200031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengpeng","family":"Zheng","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition Metabolism and Food Safety Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences  Shanghai 200031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haokai","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Nutrition and Safety College of Biotechnology Tianjin University of Science and Technology  Tianjin 300457 China"},{"name":"CAS Key Laboratory of Nutrition Metabolism and Food Safety Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences  Shanghai 200031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAS Engineering Laboratory for Nutrition Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences  Shanghai 200031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuli","family":"Yang","sequence":"additional","affiliation":[{"name":"CAS Engineering Laboratory for Nutrition Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences  Shanghai 200031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuxiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"CAS Engineering Laboratory for Nutrition Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences  Shanghai 200031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Shen","sequence":"additional","affiliation":[{"name":"Sichuan Langjiu Co. 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