{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:18:49Z","timestamp":1792801129998,"version":"4.5.0"},"reference-count":56,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/01890"],"award-info":[{"award-number":["PI18\/01890"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI22\/00514"],"award-info":[{"award-number":["PI22\/00514"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["JR23\/00042"],"award-info":[{"award-number":["JR23\/00042"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008061","name":"Fundaci\u00f3n Mutua Madrile\u00f1a","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008061","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["ED341b 2017\/19"],"award-info":[{"award-number":["ED341b 2017\/19"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["ED431B 2020\/37"],"award-info":[{"award-number":["ED431B 2020\/37"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Asociaci\u00f3n Internacional de Familiares y Afectados de Lipodistrofias"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Seipin, a protein encoded by the BSCL2 gene, plays a crucial role in lipid metabolism, and some pathogenic biallelic variants cause lipodystrophy and associated metabolic disorders. This study investigates liver pathology and dysregulation of the FGF21 signalling pathway in two mouse models: Bscl2\u2212\/\u2212 (knock-out) and Bscl2Celia\/Celia (knock-in). We evaluated liver histopathology using H&amp;E and Oil red O staining, assessed hepatic triglyceride levels via enzymatic assays, and analyzed gene expression of key FGF21-related components (Fgf21, Ppargc1a, Fgfr1, and Klb) using quantitative real-time PCR. The liver histology was scored using the NAFLD activity score (NAS) system. Both models exhibited hepatic steatosis and inflammatory features. The Bscl2\u2212\/\u2212 mice showed more pronounced liver damage, including ballooning degeneration and fibrosis. Gene expression analysis revealed a significant increase in Fgf21 in both models, suggesting an adaptive response to liver injury. Notably, Fgfr1 and Ppargc1a expression was moderately elevated in severe neurologically affected mice showing less hepatic involvement, suggesting a potential adaptive or protective association of these genes with reduced steatosis. Seipin deficiency leads to metabolic-associated steatotic liver disease and dysregulated FGF21 signalling. These findings provide insight into the pathophysiological mechanisms of lipodystrophy and liver disease and suggest that the FGF21 pathway could be a therapeutic target for treating seipin-related metabolic disorders.<\/jats:p>","DOI":"10.3390\/ijms262412037","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T09:36:39Z","timestamp":1765791399000},"page":"12037","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Metabolic-Associated Steatotic Liver Disease and FGF21 Dysregulation in Seipin-Deficient and BSCL2-Associated Celia\u2019s Encephalopathy Murine Models"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0941-626X","authenticated-orcid":false,"given":"Silvia","family":"Cobelo-G\u00f3mez","sequence":"first","affiliation":[{"name":"UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, Instituto de Investigaci\u00f3n Sanitaria Santiago de Compostela\u2014Center for Research in Molecular Medicine and Chronic Diseases (IDIS-CIMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8029-9983","authenticated-orcid":false,"given":"L\u00eda","family":"Garc\u00eda-Formoso","sequence":"additional","affiliation":[{"name":"UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, Instituto de Investigaci\u00f3n Sanitaria Santiago de Compostela\u2014Center for Research in Molecular Medicine and Chronic Diseases (IDIS-CIMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1268-7538","authenticated-orcid":false,"given":"Ant\u00eda","family":"Fern\u00e1ndez-Pombo","sequence":"additional","affiliation":[{"name":"UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, Instituto de Investigaci\u00f3n Sanitaria Santiago de Compostela\u2014Center for Research in Molecular Medicine and Chronic Diseases (IDIS-CIMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4646-6423","authenticated-orcid":false,"given":"H\u00e9ctor","family":"L\u00e1zare-Iglesias","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Clinical Hospital of Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5202-638X","authenticated-orcid":false,"given":"Everardo","family":"D\u00edaz-L\u00f3pez","sequence":"additional","affiliation":[{"name":"UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, Instituto de Investigaci\u00f3n Sanitaria Santiago de Compostela\u2014Center for Research in Molecular Medicine and Chronic Diseases (IDIS-CIMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2588-7608","authenticated-orcid":false,"given":"Teresa","family":"Prado-Mora\u00f1a","sequence":"additional","affiliation":[{"name":"UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, Instituto de Investigaci\u00f3n Sanitaria Santiago de Compostela\u2014Center for Research in Molecular Medicine and Chronic Diseases (IDIS-CIMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1836-1309","authenticated-orcid":false,"given":"Laura","family":"Rodr\u00edguez-Sobrino","sequence":"additional","affiliation":[{"name":"UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, Instituto de Investigaci\u00f3n Sanitaria Santiago de Compostela\u2014Center for Research in Molecular Medicine and Chronic Diseases (IDIS-CIMUS), University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3541-242X","authenticated-orcid":false,"given":"Ana","family":"Senra","sequence":"additional","affiliation":[{"name":"CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS, 15782 Santiago de 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