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Here, the role of hepatic c\u2010Fos in the pathophysiology of metabolic dysfunction\u2010associated steatotic liver disease and hepatocellular carcinoma (HCC) is investigated. In chow\u2010fed mice, hepatic c\u2010Fos is induced by insulin after feeding and suppressed by glucagon during fasting. Adenovirus\u2010mediated hepatic c\u2010Fos ectopic expression is sufficient to induce insulin resistance in chow\u2010fed mice. In models of diet\u2010induced obesity and inducible hepatocyte\u2010specific\n                    <jats:italic>Fos<\/jats:italic>\n                    \u2010expressing mice, elevated c\u2010Fos expression is associated with transcriptomic changes in PPAR signaling and fatty acid metabolism pathways. Mechanistically, ectopic c\u2010Fos expression enhances glycolysis and activates stress\u2010related MAPK and insulin\u2010related PI3K\u2010Akt signaling, which can contribute to metabolic dysregulation. In HCC, persistent c\u2010Fos expression correlates with activation of PI3K\u2010Akt, MAPK, and calcium signaling pathways. Functional studies show that c\u2010Fos knockdown reduces proliferation and restores apoptotic sensitivity in HCC cells under lipotoxic or endoplasmic reticulum stress conditions. These findings identify c\u2010Fos as a transcriptional regulator responsive to metabolic and hormonal cues, with potential roles in liver metabolic dysfunction and tumorigenesis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202509755","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T05:26:07Z","timestamp":1759209967000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Nutritional c\u2010Fos Induction Rewires Hepatic Metabolism and Can Promote Obesity\u2010Associated Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"12","author":[{"given":"Ao","family":"Li","sequence":"first","affiliation":[{"name":"Signal Transduction and Metabolism Laboratory Faculty of Medicine Universit\u00e9 libre de Bruxelles  Brussels B\u20101070 Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo H.","family":"Gilglioni","sequence":"additional","affiliation":[{"name":"Signal Transduction and Metabolism Laboratory Faculty of Medicine Universit\u00e9 libre de Bruxelles  Brussels B\u20101070 Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wadsen","family":"St\u2010Pierre\u2010Wijckmans","sequence":"additional","affiliation":[{"name":"Signal Transduction and Metabolism Laboratory Faculty of Medicine Universit\u00e9 libre de Bruxelles  Brussels B\u20101070 Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Hosseinzadeh","sequence":"additional","affiliation":[{"name":"Signal Transduction and Metabolism Laboratory Faculty of Medicine Universit\u00e9 libre de Bruxelles  Brussels B\u20101070 Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Veyrat\u2010Durebex","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Metabolism University of Geneva  Geneva 1211 Switzerland"},{"name":"Diabetes Center of the Faculty of Medicine University of Geneva  Geneva 1211 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumeet Pal","family":"Singh","sequence":"additional","affiliation":[{"name":"Regenerative Biology Lab Institut de Recherche Interdisciplinaire en Biologie Humaine et Mol\u00e9culaire (IRIBHM) Universit\u00e9 libre de Bruxelles  Brussels B\u20101070 Belgium"},{"name":"Department of Life Sciences School of Natural Sciences Shiv Nadar Institution of Eminence  Delhi 201301 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Coppari","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology and Metabolism University of Geneva  Geneva 1211 Switzerland"},{"name":"Diabetes Center of the Faculty of Medicine University of Geneva  Geneva 1211 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Latifa","family":"Bakiri","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna  Vienna 1090 Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4642-0273","authenticated-orcid":false,"given":"Esteban N.","family":"Gurzov","sequence":"additional","affiliation":[{"name":"Signal Transduction and Metabolism Laboratory Faculty of Medicine Universit\u00e9 libre de Bruxelles  Brussels B\u20101070 Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000004"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2023.100811"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-01950-y"},{"key":"e_1_2_8_4_1","first-page":"662","volume":"15","author":"Seydel G. 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