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In this study, we investigated metabolic changes in MASLD by analysing plasma lipidomics and metabolomics profiles from 315 biopsy-characterized patients. We observed significant alterations in alanine\/serine (ala\/ser) ratio, 1-deoxysphingolipids, alanine aminotransferase (ALT), and waist\/hip ratio (whr) between patients with and without MASH. These findings highlight a close interplay between amino acid metabolism and sphingolipid biosynthesis in MASLD progression. The shift in ala\/ser ratio particularly distinguished non-MASH from borderline MASH patients, suggesting that early metabolic disruptions precede overt liver damage. Additionally, elevated branched-chain and aromatic amino acids correlated with steatosis severity, reinforcing the central role of amino acid dysregulation in MASLD. While a simple model combining ALT, ala\/ser ratio, and whr showed some potential to support risk stratification, the primary significance of our findings lies in the mechanistic insights into metabolic dysfunction. In conclusion, this study emphasizes the importance of metabolic network alterations in MASLD and points toward future opportunities for both mechanistic research and the development of supportive diagnostic strategies.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s11306-025-02359-4","type":"journal-article","created":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:56:43Z","timestamp":1762102603000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Increased 1-deoxysphingolipids caused by an altered plasma alanine to serine ratio are associated with metabolic dysfunction-associated steatotic liver disease (MASLD)"],"prefix":"10.1007","volume":"21","author":[{"given":"F.","family":"Wipfli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9710-775X","authenticated-orcid":false,"given":"M.","family":"A. 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Journal of Biological Chemistry, 284, 4786\u20134795.","journal-title":"Journal of Biological Chemistry"}],"container-title":["Metabolomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11306-025-02359-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11306-025-02359-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11306-025-02359-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T12:01:41Z","timestamp":1764417701000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11306-025-02359-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,2]]},"references-count":48,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2359"],"URL":"https:\/\/doi.org\/10.1007\/s11306-025-02359-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7435578\/v1","asserted-by":"object"}]},"ISSN":["1573-3890"],"issn-type":[{"value":"1573-3890","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,2]]},"assertion":[{"value":"22 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"S.F. has received grants from Astellas, Falk Pharma, Genfit, Gilead Sciences, GlympsBio, Janssens Pharmaceutica, Inventiva, Merck Sharp & Dome, Pfizer, Roche.\u00a0He has acted as consultant for Abbvie, Actelion, Aelin Therapeutics, AgomAb, Aligos Therapeutics, Allergan, Alnylam, Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristoll-Meyers Squibb, CSL Behring, Coherus, Echosens, Dr. Falk Pharma, Eisai, Enyo, Galapagos, Galmed, Genetech, Genfit, Genflow Biosciences, Gilead Sciences, Intercept, Inventiva, Janssens Pharmaceutica, PRO.MED.CS Praha, Julius Clinical, Madrigal, Medimmune, Merck Sharp & Dome, Mursla Bio, NGM Bio, Novartis, Novo Nordisk, Promethera, Roche, Siemens Healthineers.\u00a0SF has been lecturer for Abbvie, Allergan, Bayer, Eisai, Genfit, Gilead Sciences, Janssens Cilag, Intercept, Inventiva, Merck Sharp & Dome, Novo Nordisk, Promethera, Siemens.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study complies with the Declaration of Helsinki and was performed according to ethics committee approval. All participant have given a written informed consent. The study approval was granted by the Ethics Committee of the Antwerp University Hospital (reference 6\/25\/125, Belgian registration number B30020071389).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"157"}}