{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T07:25:51Z","timestamp":1787124351438,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Resmetirom is a liver\u2010directed, thyroid hormone receptor \u03b2 (THR\u03b2)\u2010selective agonist approved for treating metabolic\u2010associated steatohepatitis (MASH). While Resmetirom hepatocyte\u2010specific effects are well\u2010established, its impact on other hepatic cells, particularly hepatic stellate cells (HSCs), the main fibrogenic cells, remains unknown.<\/jats:p>\n                  <jats:p>Using animal models, immortalized cell lines, and primary murine and human HSCs, we combined pharmacological treatments with genetic manipulation of THR\u03b1 and fatty acid amide hydrolase (FAAH) to examine the effects of Resmetirom. Resmetirom ameliorates MASH through actions in both hepatocytes and HSCs. The overexpression of solute carrier organic anion transporter family member 1B1(SLCO1\u03b21) in both cell types increases the efficiency of Resmetirom. THR\u03b1 expression is higher in HSCs than in hepatocytes in both human and murine cells. Resmetirom attenuates TGF\u2010\u03b21\u2010induced HSC activation via THR\u03b1 and increased FAAH expression and activity, while their inhibition prevents Resmetirom from reducing fibrotic marker expression and the elevated glycolytic activity typical of activated HSCs.<\/jats:p>\n                  <jats:p>These results uncover an unrecognized mechanism of action for Resmetirom, demonstrating that its antifibrotic efficacy extends beyond hepatocytes to include direct effects on HSCs via THR\u03b1 and FAAH. These results may support the development of future therapeutic strategies aimed at THR\u03b1 in HSC, in combination with existing approaches targeting hepatocyte THR\u03b2.<\/jats:p>","DOI":"10.1002\/mco2.70901","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T07:30:12Z","timestamp":1785915012000},"source":"Crossref","is-referenced-by-count":0,"title":["Resmetirom Ameliorates Fibrogenesis in Hepatic Stellate Cells via Thyroid Hormone Receptor Alpha\u2010Fatty\u2010Acid Amide Hydrolase 1 Signaling Pathway"],"prefix":"10.1002","volume":"7","author":[{"given":"Eva","family":"Novoa","sequence":"first","affiliation":[{"name":"Department of Physiology, CIMUS University of Santiago de Compostela  Santiago de Compostela Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBERobn)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Cabaleiro","sequence":"additional","affiliation":[{"name":"Department of Physiology, CIMUS University of Santiago de Compostela  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borja","family":"L\u00f3pez\u2010Picallo","sequence":"additional","affiliation":[{"name":"Department of Physiology, CIMUS University of Santiago de Compostela  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia da Silva","family":"Lima","sequence":"additional","affiliation":[{"name":"Regulation of Gene Expression and Applications (EXPRELA) Group, Interdisciplinary Centre for Chemistry and Biology \u2013 CICA, University of Coru\u00f1a  A Coru\u00f1a Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Riobello","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology CIMUS, IDIS, Universidade de Santiago de Compostela  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Pena","sequence":"additional","affiliation":[{"name":"Proteomic Unit, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela  A Coru\u00f1a Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Iglesias\u2010Moure","sequence":"additional","affiliation":[{"name":"Department of Physiology, CIMUS University of Santiago de Compostela  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Senra","sequence":"additional","affiliation":[{"name":"Department of Physiology, CIMUS University of Santiago de Compostela  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luz","family":"Mart\u00ednez\u2010Chantar","sequence":"additional","affiliation":[{"name":"Liver Disease Lab, BRTA CIC bioGUNE, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd)  Derio Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anabel","family":"Fernandez\u2010Iglesias","sequence":"additional","affiliation":[{"name":"Liver Research Unit, Institut de Recerca Biom\u00e8dica Catalunya Sud (IRBCatSud), Hospital Universitari Joan 23 de Tarragona \u2010 CIBEREHD  Tarragona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Gracia\u2010Sancho","sequence":"additional","affiliation":[{"name":"Liver Research Unit, Institut de Recerca Biom\u00e8dica Catalunya Sud (IRBCatSud), Hospital Universitari Joan 23 de Tarragona \u2010 CIBEREHD  Tarragona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Bravo","sequence":"additional","affiliation":[{"name":"Proteomic Unit, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela  A Coru\u00f1a Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Dieguez","sequence":"additional","affiliation":[{"name":"Department of Physiology, CIMUS University of Santiago de Compostela  Santiago de Compostela Spain"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n (CIBERobn)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Varela\u2010Rey","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology CIMUS, IDIS, Universidade de Santiago de Compostela  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Prevot","sequence":"additional","affiliation":[{"name":"Laboratory of Development and Plasticity of the Neuroendocrine Brain, Univ. 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