biostudies-literatureDheedene WCosmetics Europe/European Commission FP7 GrantEuropean Research CouncilKU Leuven (Katholieke Universiteit Leuven)EC | EC Seventh Framework Programm | FP7 People: Marie-Curie Actions (FP7-PEOPLE - Specific Programme "People" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))EC | EU Framework Programme for Research and Innovation H2020 | H2020 Excellent Science (H2020 Priority Excellent Science)Erasmus University Rotterdam | Erasmus Universitair Medisch Centrum Rotterdam (Erasmus Universitair Medisch Centrum)ZonMwInteruniversity Attraction Poles GrantFonds Wetenschappelijk Onderzoek (Research Foundation Flanders)23434https://www.ebi.ac.uk/biostudies/studies/S-EPMC12222841biostudies-literatureUnknown15(1)Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, features liver sinusoidal endothelial cell (LSEC) alterations with ill-defined driving factors. Zinc-Finger E-Box-binding Homeobox (ZEB)2 in LSECs preserves their specialized features, prevents capillarization and protects against liver fibrosis. To investigate a potential protective role against steatosis, the initial MASLD stage, we fed EC-specific Zeb2 knockout (EC^Zeb2KO) mice a western-type diet (WD). In healthy and steatotic wild-type livers, Zeb2 was ubiquitously and similarly expressed across blood-vascular EC types. LSEC RNA sequencing revealed ZEB2 deficiency-triggered expression changes greatly overlapping with those evoked by WD-feeding. Endothelial ZScientific reportsLoss of endothelial ZEB2 in mice attenuates steatosis early during metabolic dysfunction-associated steatotic liver disease.PMC12222841departmental funds1S25817NC14/19/095IUAP/P7/072018/23115|ZONMWH2020-MSCA-IF-REZONABLE658666FP7-StG-IMAGINED2032911157318N1243121NC12/16/023PF/10/014H2020 848109-CRUCIAL848109FP7-Health-HemiBio266777WOG001420NG.0A3116BIG project fundingDemuynck LLox Mvan IJcken WFJStroobants MJones EAVJacquemin Mde Haan WVan Wauwe JHuylebroeck Dvan Grunsven LADheedene WZwijsen AVinckier SVandervoort PLavend'homme RMartinod KVerhulst SLuttun ACallewaert BMulugeta EfalseLoss of endothelial ZEB2 in mice attenuates steatosis early during metabolic dysfunction-associated steatotic liver disease.Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, features liver sinusoidal endothelial cell (LSEC) alterations with ill-defined driving factors. Zinc-Finger E-Box-binding Homeobox (ZEB)2 in LSECs preserves their specialized features, prevents capillarization and protects against liver fibrosis. To investigate a potential protective role against steatosis, the initial MASLD stage, we fed EC-specific Zeb2 knockout (EC^Zeb2KO) mice a western-type diet (WD). In healthy and steatotic wild-type livers, Zeb2 was ubiquitously and similarly expressed across blood-vascular EC types. LSEC RNA sequencing revealed ZEB2 deficiency-triggered expression changes greatly overlapping with those evoked by WD-feeding. Endothelial Z2025-01-01T00:00:00Z2025 Jul2026-06-02T08:45:00.948Z2026-04-16T03:12:51.747ZS-EPMC122228414060396610.1038/s41598-025-05881-6