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To date, the molecular mechanisms and enzymes mediating the loss of hepatic vitamin A stores are incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>\n                      Using a fibrosis mouse model induced by the hepatotoxin carbon tetrachloride (CCl\n                      <jats:sub>4<\/jats:sub>\n                      ), we investigated which cellular processes in the liver mediate the loss of hepatic retinyl ester stores. We found that repeated CCl\n                      <jats:sub>4<\/jats:sub>\n                      injections into mice over six\u2009weeks led to a biphasic change in plasma retinol levels that were increased after three and decreased after six\u2009weeks as compared to control mice. As expected, livers of mice receiving CCl\n                      <jats:sub>4<\/jats:sub>\n                      injections showed increased expression of pro\u2010fibrogenic genes that were accompanied by decreased hepatic retinoid content, which was mainly due to loss of retinoids in non\u2010parenchymal cells (NPCs). In the liver and NPCs, decreased retinyl ester levels correlated with reduced gene expression of lecithin:retinol acyltransferase and reduced hepatic ex\u00a0vivo retinol acyltransferase activity. Conversely, gene expression of lipases known to exhibit retinyl ester hydrolase activity (REHA) remained unchanged or was decreased, consistent with decreased neutral REHA in homogenates of respective livers and lysates of isolated NPCs, respectively. Albeit hepatic expression levels of marker proteins for autophagosomal and lysosomal membranes were increased, gene expression of the major acidic retinyl ester hydrolase, lysosomal acid lipase, as well as ex\u00a0vivo acidic REHA were reduced in NPC lysates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together, these results indicate that the loss of hepatic retinyl ester stores upon liver injury and stellate cell activation is rather a consequence of reduced retinol esterification than neutral or acidic hydrolysis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70213","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T13:15:25Z","timestamp":1754486125000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Reduced Esterification 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