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Autophagy is an essential catabolic pathway and blocked autophagy may result in abnormal lipid metabolism in liver. A body of evidence demonstrates that Pb exposure causes abnormal lipid droplet (LDs) accumulation in the liver, but the mechanism remains unknown. Here, we investigated whether Pb induced lipid accumulation by regulating autophagy in HepG2 cells. In this study, we found that Pb (50\u2009\u03bcM) blocked the autophagy flux mainly by transcription factor EB (TFEB)\u2010mediated impairment of lysosome formation and activity. Then we demonstrated that the dense lipid accumulation was observed upon Pb exposure, and induction of autophagy by the autophagy activator rapamycin (Rap) alleviated Pb\u2010induced lipid accumulation, while suppression of autophagy by chloroquine (CQ) exacerbated Pb\u2010induced lipid accumulation, suggested that Pb\u2010induced autophagy blockage might be responsible for lipid accumulation. Moreover, we demonstrated that the SIRT1\/mTOR pathway participated in Pb\u2010induced autophagy dysregulation, leading to Pb\u2010induced hepatic lipid accumulation. In summary, these results revealed a new insight into the relationship between Pb\u2010caused autophagy dysregulation and lipid accumulation for the first time and highlight autophagy as a novel therapeutic target against Pb\u2010induced hepatic lipid accumulation which supplying the theoretical basis and potential strategies for the intervention and treatment of Pb\u2010related disease.<\/jats:p>","DOI":"10.1002\/tox.23420","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T11:51:54Z","timestamp":1638186714000},"page":"549-563","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<scp>SIRT1<\/scp>\/<scp>mTOR<\/scp> pathway\u2010mediated autophagy dysregulation promotes Pb\u2010induced hepatic lipid accumulation in <scp>HepG2<\/scp> cells"],"prefix":"10.1002","volume":"37","author":[{"given":"Yanan","family":"Zhao","sequence":"first","affiliation":[{"name":"College of Food Science 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