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Mol. Life Sci."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; aims<\/jats:title>\n                    <jats:p>Abnormal cholesterol metabolism is involved in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the role and mechanisms of lanosterol synthase (LSS) loss of function in the pathological process of MASLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      MASLD models were induced by methionine-and choline-deficient diet (MCD) feeding in LSS\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      mice or wild type mice given LSS inhibitor RO48-8071. Transcriptomics analysis was performed to analyze differentially expressed genes in mice model. Lipidomic Profiling revealed the overall composition of lipid classes in MCD induced MASLD model. In vitro experiments using a MCDE (identical medium completely deficient of methionine and choline) induced cell model assessed the effect of LSS knockdown on MASLD development. Quantitative real-time PCR (qRT-PCR) and Western blot were employed to evaluate the differential expression of interested genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In MCD induced MASLD models, obviously reduced steatotic phenotype, hepatic inflammatory injury and hepatocyte ballooning were found in LSS\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      mice. LSS loss of function alleviates liver injury and hepatic steatosis via reducing fatty deposition and triglyceride accumulation in hepatocytes. Mechanistically, LSS dysfunction promotes fatty acid \u03b2-oxidation and ketogenesis in liver cells to mediate attenuating effect on MASLD development.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Targeting LSS alleviates MASLD development by promoting fatty acid \u03b2-oxidation and ketogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00018-026-06091-7","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T18:53:21Z","timestamp":1773773601000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting lanosterol synthase alleviates MASLD by promoting fatty acid catabolism"],"prefix":"10.1007","volume":"83","author":[{"given":"Sumei","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingcong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dake","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weikang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhai","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yechuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6098-1208","authenticated-orcid":false,"given":"Shengquan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"issue":"6","key":"6091_CR1","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1097\/hep","volume":"78","author":"ME Rinella","year":"2023","unstructured":"Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F et al (2023) A multisociety Delphi consensus statement on new fatty liver disease nomenclature. 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