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Treating mice with antisense oligonucleotides against\n                    <jats:italic toggle=\"yes\">\n                      Coenzyme A synthase (\n                      <jats:italic toggle=\"yes\">Coasy<\/jats:italic>\n                      )\n                    <\/jats:italic>\n                    or treatment with bempedoic acid or atorvastatin decreased liver lipid droplet cholesterol content and prevented CDAHFD-induced MASH and the fibrotic response. All these salutary effects were abrogated with dietary cholesterol supplementation. Analysis of human liver samples demonstrated that cholesterol in liver lipid droplets was increased in humans with MASH and liver fibrosis and was higher in PNPLA3 I148M (variants rs738409) than in HSD17B13 variants (rs72613567). Together, these data identify cholesterol in liver lipid droplets as a critical mediator of MASH and demonstrate that Coenzyme A synthase knockdown and bempedoic acid are therapeutic approaches to reduce liver lipid droplet cholesterol content and thereby prevent the development of MASH and liver fibrosis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2502978122","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T10:49:28Z","timestamp":1746096568000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":48,"title":["Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction\u2013associated steatohepatitis"],"prefix":"10.1073","volume":"122","author":[{"given":"Ikki","family":"Sakuma","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Yale School of Medicine","place":["New Haven"]},{"name":"Department of Molecular Diagnosis, Chiba University 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