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The progression of MASLD involves interconnected pathways including dysregulated de novo lipogenesis, insulin resistance, mitochondrial dysfunction, gut dysbiosis, ferroptosis, and genetic and epigenetic predispositions. These mechanisms not only promote hepatic injury but also accelerate atherosclerosis. Notably, MASLD exhibits significant sexual dimorphism, influenced by physiological differences, sex hormones, genetic factors, and the microbiome. The study of these complex processes relies mostly on dietary-induced animal models, particularly in rats, which effectively recapitulate features of the human disease. Given the multifaceted nature of MASLD, the therapeutic focus is shifting from monotherapies to combination or dual-target strategies. To enable this transition, refinement of preclinical models is essential to better understand and target this complex disorder.<\/jats:p>","DOI":"10.3390\/nu18040679","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T15:57:29Z","timestamp":1771516649000},"page":"679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A Global Perspective on Metabolic Dysfunction-Associated Steatotic Liver Disease: From Molecular Mechanisms to Therapeutic Strategy Innovation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0077-6682","authenticated-orcid":false,"given":"Yanhao","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7082-0704","authenticated-orcid":false,"given":"Juan Carlos","family":"Laguna","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Institute of Biomedicine, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5652-8651","authenticated-orcid":false,"given":"Marta","family":"Alegret","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Institute of Biomedicine, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laia","family":"Vil\u00e0","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute of Biomedicine, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"117523","DOI":"10.1016\/j.atherosclerosis.2024.117523","article-title":"Metabolic dysfunction-associated steatotic liver disease: An opportunity for collaboration between cardiology and hepatology","volume":"392","author":"Raggi","year":"2024","journal-title":"Atherosclerosis"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1097\/HEP.0000000000000520","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"78","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1038\/s42255-021-00501-9","article-title":"Non-alcoholic fatty liver disease: The interplay between metabolism, microbes and immunity","volume":"3","author":"Tilg","year":"2021","journal-title":"Nat. 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