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Simvastatin (SV) has been shown to ameliorate liver fibrosis; however, its underlying mechanisms remain unclear. This study aimed to explore the protective effects of SV on liver fibrosis with a focus on metabolic regulation. A carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    )\u2010induced liver fibrosis model was established in mice, and SV was administered via gavage. LX\u20102 cells were used for in\u00a0vitro mechanistic studies. Our findings demonstrated that SV effectively suppressed aerobic glycolysis and glutaminolysis in activated HSCs. Mechanistically, SV inhibited the PKM2\/STAT3\/c\u2010MYC pathway by targeting PKM2, leading to reduced c\u2010MYC expression. This downregulation of c\u2010MYC decreased ASCT2 expression, a key transporter in glutamine metabolism, thereby impairing glutamine utilization. These results provide new insights into the metabolic regulatory mechanisms of SV in liver fibrosis and lay the foundation for further exploration of its therapeutic potential in liver disease.\n                  <\/jats:p>","DOI":"10.1096\/fj.202503580r","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T15:29:04Z","timestamp":1771601344000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Simvastatin Targets\n                    <scp>PKM2<\/scp>\n                    to Alter Metabolic Reprogramming in Hepatic Stellate Cells and Mitigate Liver Fibrosis"],"prefix":"10.1096","volume":"40","author":[{"given":"Ruoru","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang 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