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In brief, L02 cells were pretreated with or without ethanol (3%) for 24\u2009h, then treated quercetin (80, 40, 20\u2009\u03bcM) for 24\u2009h. The transfection procedure was performed with transcription factor EB (TFEB) small interfering RNA (siRNA TFEB) for 24\u2009h. Our results showed that quercetin autophagic flux in the L02 cells, via upregulating of microtubule associated protein light chain 3B (LC3\u2010II) and lysosome\u2010associated membrane protein 1 (LAMP1), then downregulating of protein sequestosome 1 (SQSTM1\/p62). Mechanistically, quercetin activated TFEB nuclear translocation, contributing to lysosomal biogenesis and autophagic activation. Accordingly, the genetic inhibition of TFEB\u2010dependent autophagy decreased ethanol\u2010induced fat accumulation in L02 cells via regulating fatty acid \u03b2 oxidation and lipid synthesis. Subsequently, quercetin\u2010induced TFEB\u2010dependent autophagic activation was also linked to inhibit oxidative stress via suppressing reactive oxygen species (ROS), enhancing activities of antioxidant enzymes, and promoting nuclear transfer of the nuclear factor E2\u2010related factor 2 (Nrf2) translocation. Thus, we uncovered a novel protective mechanism against ethanol\u2010induced hepatic steatosis and oxidative stress through TFEB\u2010mediated lysosomal biogenesis and discovered insufficient autophagy as a novel previously unappreciated autophagic flux.<\/jats:p>","DOI":"10.1002\/ptr.7593","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T04:31:06Z","timestamp":1663821066000},"page":"62-76","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Quercetin alleviates ethanol\u2010induced hepatic steatosis in <scp>L02<\/scp> cells by activating <scp>TFEB<\/scp> translocation to compensate for inadequate autophagy"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1668-0453","authenticated-orcid":false,"given":"Xingtao","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources Ministry of 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