Vacca, MicheleMicheleVaccaKamzolas, IoannisIoannisKamzolasHarder, Lea MørchLea MørchHarderOakley, FionaFionaOakleyTrautwein, ChristianChristianTrautweinHatting, MaximilianMaximilianHattingRoss, TrentonTrentonRossBernardo, BarbaraBarbaraBernardoOldenburger, AnoukAnoukOldenburgerHjuler, Sara ToftegaardSara ToftegaardHjulerKsiazek, IwonaIwonaKsiazekLindén, DanielDanielLindénSchuppan, DetlefDetlefSchuppanRodriguez-Cuenca, SergioSergioRodriguez-CuencaTonini, Maria ManuelaMaria ManuelaToniniCastañeda, Tamara RTamara RCastañedaKannt, AimoAimoKanntRodrigues, Cecília M PCecília M PRodriguesCockell, SimonSimonCockellGovaere, OlivierOlivierGovaereDaly, Ann KAnn KDalyAllison, MichaelMichaelAllisonHonnens de Lichtenberg, KristianKristianHonnens de LichtenbergKim, Yong OokYong OokKimLindblom, AnnaAnnaLindblomOldham, StephanieStephanieOldhamAndréasson, Anne-ChristineAnne-ChristineAndréassonSchlerman, FranklinFranklinSchlermanMarioneaux, JonathonJonathonMarioneauxSanyal, ArunArunSanyalAfonso, Marta BMarta BAfonsoYounes, RamyRamyYounesAmano, YuichiroYuichiroAmanoFriedman, Scott LScott LFriedmanWang, ShuangShuangWangBhattacharya, DipankarDipankarBhattacharyaSimon, EricEricSimonParadis, ValérieValérieParadisBurt, AlastairAlastairBurtGrypari, Ioanna MariaIoanna MariaGrypariDavies, SusanSusanDaviesDriessen, AnnAnnDriessenYashiro, HiroakiHiroakiYashiroPors, SusanneSusannePorsWorm Andersen, MajaMajaWorm AndersenFeigh, MichaelMichaelFeighYunis, CarlaCarlaYunisBedossa, PierrePierreBedossaStewart, MichelleMichelleStewartCater, Heather LHeather LCaterWells, SaraSaraWellsSchattenberg, Jörn MJörn MSchattenbergAnstee, Quentin MQuentin MAnsteeTiniakos, DinaDinaTiniakosPerfield, James WJames WPerfieldPetsalaki, EvangeliaEvangeliaPetsalakiDavidsen, PeterPeterDavidsenVidal-Puig, AntonioAntonioVidal-Puig2024-11-112024-11-112024-06https://boris-portal.unibe.ch/handle/20.500.12422/188865Collaborators "LITMUS Investigators": Annalisa Berzigotti (UVCM, Department of Visceral Surgery and Medicine)Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, encompasses steatosis and metabolic dysfunction-associated steatohepatitis (MASH), leading to cirrhosis and hepatocellular carcinoma. Preclinical MASLD research is mainly performed in rodents; however, the model that best recapitulates human disease is yet to be defined. We conducted a wide-ranging retrospective review (metabolic phenotype, liver histopathology, transcriptome benchmarked against humans) of murine models (mostly male) and ranked them using an unbiased MASLD 'human proximity score' to define their metabolic relevance and ability to induce MASH-fibrosis. Here, we show that Western diets align closely with human MASH; high cholesterol content, extended study duration and/or genetic manipulation of disease-promoting pathways are required to intensify liver damage and accelerate significant (F2+) fibrosis development. Choline-deficient models rapidly induce MASH-fibrosis while showing relatively poor translatability. Our ranking of commonly used MASLD models, based on their proximity to human MASLD, helps with the selection of appropriate in vivo models to accelerate preclinical research.enarticle10.48620/761453886702210.1038/s42255-024-01043-6