{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T18:15:57Z","timestamp":1778696157593,"version":"3.51.4"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>MASLD is linked to dyslipidemia, but it remains unclear whether this alteration depends more on disease activity or fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine whether dyslipidemia is primarily associated with activity and\/or fibrosis through standard lipid profile and advanced lipidomics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A cross-sectional study was conducted including patients with suspected MASLD at a single center. Intraoperative liver biopsies were obtained. Only patients with MASLD were included in the analysis. Histological activity was defined as a NAFLD Activity Score (NAS) \u22655 and fibrosis was staged according to standard criteria. Clinical, biochemical, lipoprotein, and fatty acid profiles were assessed, including nuclear magnetic resonance (NMR) spectroscopy for lipoprotein subfractions and gas chromatography for fatty acids. Multivariable linear regression models were used to evaluate independent associations of activity and fibrosis with lipid parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 49 patients were analyzed (mean age 48 years, 46% men, 94% with BMI\u2009&gt;\u200935). Liver biopsies revealed a 30.6% prevalence of activity (NAS\u2009\u2265\u20095) and 36.7% of fibrosis. Higher lipid levels in patients with activity were related to apolipoprotein B, non-HDL cholesterol, and triglycerides in both univariate and multivariate models. Fibrosis was not associated with any lipid parameter. Lipidomics confirmed associations of activity with VLDL+IDL cholesterol (\u03b2\u2009=\u20090.474, 95% CI 0.204\u20130.745, p\u2009=\u20090.001), VLDL+IDL triglycerides (\u03b2\u2009=\u20090.454, 95% CI 0.198\u20130.710, p\u2009=\u20090.001), and VLDL particle concentration (\u03b2\u2009=\u20090.409, 95% CI 0.155\u20130.663, p\u2009=\u20090.002), and showed a trend toward an inverse association with the percentage of large VLDL particles (\u03b2=\u22120.298, 95% CI \u22120.602\u20130.006, p\u2009=\u20090.054). Besides, the omega-6\/triglycerides ratio was inversely associated with activity (\u03b2=\u22120.345, 95% CI \u22120.630 to \u22120.060, p\u2009=\u20090.019).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Hepatic inflammatory activity showed strong associations with a non-traditional atherogenic lipidomic profile. These findings suggest that activity, rather than liver fibrosis, may be a key factor in the MASLD atherosclerotic momentum.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0343134","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T17:50:45Z","timestamp":1778694645000},"page":"e0343134","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of activity and fibrosis in the MASLD atherogenic momentum through advanced lipidomics"],"prefix":"10.1371","volume":"21","author":[{"given":"Agust\u00edn","family":"Blanco-Echevarr\u00eda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8423-3378","authenticated-orcid":true,"given":"Ram\u00f3n","family":"Costa Segovia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8132-9366","authenticated-orcid":true,"given":"Carlos","family":"Guijarro Herraiz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bel\u00e9n","family":"Garc\u00eda Izquierdo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonsoles","family":"Guadalix","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes","family":"P\u00e9rez Carreras","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4811-5486","authenticated-orcid":true,"given":"Yolanda","family":"Rodr\u00edguez Gil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"de Castro Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0116-9145","authenticated-orcid":true,"given":"Nuria","family":"Amig\u00f3","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delia","family":"D\u2019Avola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Lumbreras Bermejo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0530-7349","authenticated-orcid":true,"given":"Diego","family":"Mart\u00ednez-Urbistondo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"issue":"4","key":"pone.0343134.ref001","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1136\/gutjnl-2023-330595","article-title":"MASLD: a systemic metabolic disorder with cardiovascular and malignant complications","volume":"73","author":"G Targher","year":"2024","journal-title":"Gut"},{"issue":"1","key":"pone.0343134.ref002","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention","volume":"15","author":"Z Younossi","year":"2018","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"10","key":"pone.0343134.ref003","doi-asserted-by":"crossref","DOI":"10.1111\/eci.14036","article-title":"Estimation of fatty liver disease clinical role on glucose metabolic remodelling phenotypes and T2DM onset","volume":"53","author":"D Martinez-Urbistondo","year":"2023","journal-title":"Eur J Clin Invest"},{"issue":"5","key":"pone.0343134.ref004","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1002\/hep.27368","article-title":"Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up","volume":"61","author":"M Ekstedt","year":"2015","journal-title":"Hepatology"},{"issue":"1","key":"pone.0343134.ref005","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/liv.13973","article-title":"Cardiovascular risk factors in non-alcoholic fatty liver disease","volume":"39","author":"H Hagstr\u00f6m","year":"2019","journal-title":"Liver Int"},{"issue":"9","key":"pone.0343134.ref006","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1136\/gutjnl-2021-325724","article-title":"Non-alcoholic fatty liver disease and incident major adverse cardiovascular events: results from a nationwide histology cohort","volume":"71","author":"TG Simon","year":"2022","journal-title":"Gut"},{"issue":"1","key":"pone.0343134.ref007","doi-asserted-by":"crossref","first-page":"11124","DOI":"10.1038\/s41598-019-47687-3","article-title":"Nonalcoholic fatty liver disease and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis","volume":"9","author":"Y Liu","year":"2019","journal-title":"Sci Rep"},{"issue":"11","key":"pone.0343134.ref008","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/S2468-1253(21)00308-3","article-title":"Non-alcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: an updated systematic review and meta-analysis","volume":"6","author":"A Mantovani","year":"2021","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"pone.0343134.ref009","article-title":"Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults","volume":"367","author":"M Alexander","year":"2019","journal-title":"BMJ"},{"issue":"34","key":"pone.0343134.ref010","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1093\/eurheartj\/ehab484","article-title":"2021 ESC Guidelines on cardiovascular disease prevention in clinical practice","volume":"42","author":"FLJ Visseren","year":"2021","journal-title":"Eur Heart J"},{"issue":"12","key":"pone.0343134.ref011","doi-asserted-by":"crossref","first-page":"3624","DOI":"10.1038\/s41591-024-03283-1","article-title":"Data-driven cluster analysis identifies distinct types of metabolic dysfunction-associated steatotic liver disease","volume":"30","author":"V Raverdy","year":"2024","journal-title":"Nat Med"},{"issue":"2","key":"pone.0343134.ref012","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3390\/biom15020163","article-title":"Metabolic dysfunction-associated steatotic liver disease: pathogenetic links to cardiovascular risk","volume":"15","author":"VA Ionescu","year":"2025","journal-title":"Biomolecules"},{"issue":"7","key":"pone.0343134.ref013","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1136\/gutjnl-2020-322786","article-title":"Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort","volume":"70","author":"TG Simon","year":"2021","journal-title":"Gut"},{"issue":"6","key":"pone.0343134.ref014","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1016\/j.jhep.2017.09.024","article-title":"Back to Byzance: Querelles byzantines over NASH and fibrosis","volume":"67","author":"V Ratziu","year":"2017","journal-title":"J Hepatol"},{"issue":"9","key":"pone.0343134.ref015","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1111\/jgh.15523","article-title":"Interplay between non-alcoholic fatty liver disease and cardiovascular risk in an asymptomatic general population","volume":"36","author":"G Pennisi","year":"2021","journal-title":"J Gastroenterol Hepatol"},{"key":"pone.0343134.ref016","article-title":"2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024","volume":"47","author":"American Diabetes Association Professional Practice Committee","year":"2024","journal-title":"Diabetes Care"},{"issue":"1","key":"pone.0343134.ref017","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/eurheartj\/ehz455","article-title":"2019 ESC\/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk","volume":"41","author":"F Mach","year":"2020","journal-title":"Eur Heart J"},{"issue":"10","key":"pone.0343134.ref018","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/j.jacc.2018.06.046","article-title":"Impact of Lipids on Cardiovascular Health: JACC Health Promotion Series","volume":"72","author":"BA Ference","year":"2018","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"pone.0343134.ref019","first-page":"45","article-title":"Clinical implications of discordance between LDL cholesterol and particle number","volume":"16","author":"JD Otvos","year":"2022","journal-title":"J Clin Lipidol"},{"issue":"3","key":"pone.0343134.ref020","article-title":"Biomarkers of dietary omega fatty acids and incident cardiovascular disease","volume":"12","author":"M Marklund","year":"2023","journal-title":"J Am Heart Assoc"},{"issue":"2","key":"pone.0343134.ref021","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.atherosclerosis.2014.01.034","article-title":"Comparison of four methods of analysis of lipoprotein particle subfractions for their association with angiographic progression of coronary artery disease","volume":"233","author":"PT Williams","year":"2014","journal-title":"Atherosclerosis"},{"issue":"11","key":"pone.0343134.ref022","article-title":"The lipoprotein profile evaluated by 1H-NMR Improves the performance of genetic testing in familial hypercholesterolemia","volume":"109","author":"I Daiana","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"pone.0343134.ref023","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/S0022-2275(20)38861-1","article-title":"Direct transesterification of all classes of lipids in a one-step reaction","volume":"27","author":"G Lepage","year":"1986","journal-title":"J Lipid Res"},{"issue":"3","key":"pone.0343134.ref024","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1194\/jlr.D001065","article-title":"Preparation of fatty acid methyl esters for gas-liquid chromatography","volume":"51","author":"K Ichihara","year":"2010","journal-title":"J Lipid Res"},{"issue":"7","key":"pone.0343134.ref025","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/s11883-022-01028-4","article-title":"Management of dyslipidemia in patients with non-alcoholic fatty liver disease","volume":"24","author":"A Martin","year":"2022","journal-title":"Curr Atheroscler Rep"},{"issue":"12","key":"pone.0343134.ref026","first-page":"443","article-title":"Comprehensive review of cardiovascular disease risk in nonalcoholic fatty liver disease","volume":"9","author":"K Josloff","year":"2022","journal-title":"J Cardiovasc Dev Dis"},{"issue":"6","key":"pone.0343134.ref027","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1073\/pnas.0630588100","article-title":"Triglyceride accumulation protects against fatty acid-induced lipotoxicity","volume":"100","author":"LL Listenberger","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"pone.0343134.ref028","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1111\/brv.12178","article-title":"De novo lipogenesis in the liver in health and disease: more than just a shunting yard for glucose","volume":"91","author":"FWB Sanders","year":"2016","journal-title":"Biol Rev Camb Philos Soc"},{"issue":"11","key":"pone.0343134.ref029","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.biochi.2004.09.018","article-title":"SREBP transcription factors: master regulators of lipid homeostasis","volume":"86","author":"D Eberl\u00e9","year":"2004","journal-title":"Biochimie"},{"issue":"6","key":"pone.0343134.ref030","doi-asserted-by":"crossref","DOI":"10.1097\/HC9.0000000000000716","article-title":"VLDL lipidomics reveals hepatocellular lipidome changes in metabolic dysfunction-associated steatotic liver disease","volume":"9","author":"D Guardamino Ojeda","year":"2025","journal-title":"Hepatol Commun"},{"issue":"4","key":"pone.0343134.ref031","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.jhep.2021.05.008","article-title":"Long-term outcomes and predictive ability of non-invasive scoring systems in patients with non-alcoholic fatty liver disease","volume":"75","author":"R Younes","year":"2021","journal-title":"J Hepatol"},{"issue":"7","key":"pone.0343134.ref032","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1111\/apt.15660","article-title":"Advanced fibrosis is associated with incident cardiovascular disease in patients with non-alcoholic fatty liver disease","volume":"51","author":"JB Henson","year":"2020","journal-title":"Aliment Pharmacol Ther"},{"key":"pone.0343134.ref033","doi-asserted-by":"crossref","first-page":"1721278","DOI":"10.3389\/fendo.2025.1721278","article-title":"Hypersensitive C-reactive protein-atherogenic index as a novel marker for metabolic dysfunction-associated steatotic liver disease in type 2 diabetes mellitus","volume":"16","author":"W Wang","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"key":"pone.0343134.ref034","doi-asserted-by":"crossref","first-page":"120557","DOI":"10.1016\/j.atherosclerosis.2025.120557","article-title":"Fatty liver-index, systemic inflammation and cardiovascular mortality. Results from the LURIC study","volume":"411","author":"S Wissel","year":"2025","journal-title":"Atherosclerosis"},{"issue":"17","key":"pone.0343134.ref035","doi-asserted-by":"crossref","first-page":"5190","DOI":"10.3390\/jcm11175190","article-title":"Interactive role of surrogate liver fibrosis assessment and insulin resistance on the incidence of major cardiovascular events","volume":"11","author":"D Martinez-Urbistondo","year":"2022","journal-title":"J Clin Med"},{"issue":"7","key":"pone.0343134.ref036","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1002\/hep4.1188","article-title":"Metabolomic-based noninvasive serum test to diagnose nonalcoholic steatohepatitis: Results from discovery and validation cohorts","volume":"2","author":"R Mayo","year":"2018","journal-title":"Hepatol Commun"},{"issue":"1","key":"pone.0343134.ref037","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/j.2040-4603.2018.tb00008.x","article-title":"Triglyceride metabolism in the liver","volume":"8","author":"M Alves-Bezerra","year":"2017","journal-title":"Compr Physiol"},{"issue":"4","key":"pone.0343134.ref038","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1056\/NEJMoa2401943","article-title":"Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis","volume":"391","author":"R Loomba","year":"2024","journal-title":"N Engl J Med"},{"issue":"21","key":"pone.0343134.ref039","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1056\/NEJMoa2413258","article-title":"Phase 3 trial of semaglutide in metabolic dysfunction-associated steatohepatitis","volume":"392","author":"AJ Sanyal","year":"2025","journal-title":"N Engl J Med"},{"issue":"6","key":"pone.0343134.ref040","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1056\/NEJMoa2309000","article-title":"A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis","volume":"390","author":"SA Harrison","year":"2024","journal-title":"N Engl J Med"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0343134","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T17:50:52Z","timestamp":1778694652000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0343134"}},"subtitle":[],"editor":[{"given":"Marwan Salih","family":"Al-Nimer","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":40,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0343134","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,13]]}}}