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Identifying effective and safe natural compounds that target lipophagy to eliminate excess lipids may be a potential therapeutic strategy for non\u2010alcoholic fatty liver disease (NAFLD). Here the effects of naringin on NAFLD and the underlying mechanisms involved are investigated. Naringin treatment effectively relieves HFD\u2010induced hepatic steatosis in mice and inhibits PA\u2010induced lipid accumulation in hepatocytes. Increased p62 and LC3\u2010II levels are observed with excess lipid support autophagosome accumulation and impaired autophagic flux. Treatment with naringin restores TFEB\u2010mediated lysosomal biogenesis, thereby promoting the fusion of autophagosomes and lysosomes, restoring impaired autophagic flux and further inducing lipophagy. However, the knockdown of TFEB in hepatocytes or the hepatocyte\u2010specific knockout of TFEB in mice abrogates naringin\u2010induced lipophagy, eliminating its therapeutic effect on hepatic steatosis. These results demonstrate that TFEB\u2010mediated lysosomal biogenesis and subsequent lipophagy play essential roles in the ability of naringin to mitigate hepatic steatosis and suggest that naringin is a promising drug for treating NAFLD.<\/jats:p>","DOI":"10.1002\/mnfr.202200812","type":"journal-article","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T18:22:02Z","timestamp":1701886922000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Naringin Protects against Non\u2010Alcoholic Fatty Liver Disease by Promoting Autophagic Flux and Lipophagy"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0025-5209","authenticated-orcid":false,"given":"Lingling","family":"Guan","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences North China University of Science and Technology  Tangshan 063000 China"},{"name":"Beijing Key Laboratory for 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