An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD)
Authors: Vacca Michele , Kamzolas Ioannis , Harder Lea Mørch , Oakley Fiona , Trautwein Christian , Hatting Maximilian , Ross Trenton , Bernardo Barbara , Oldenburger Anouk , Hjuler Sara Toftegaard , Ksiazek Iwona , Lindén Daniel , Schuppan Detlef , Rodriguez-Cuenca Sergio , Tonini Maria Manuela , Castañeda Tamara R. , Kannt Aimo , Rodrigues Cecília M. P. , Cockell Simon , Govaere Olivier , Daly Ann K. , Allison Michael , Honnens de Lichtenberg Kristian , Kim Yong Ook , Lindblom Anna , Oldham Stephanie , Andréasson Anne-Christine , Schlerman Franklin , Marioneaux Jonathon , Sanyal Arun , Afonso Marta B. , Younes Ramy , Amano Yuichiro , Friedman Scott L. , Wang Shuang , Bhattacharya Dipankar , Simon Eric , Paradis Valérie , Burt Alastair , Grypari Ioanna Maria , Davies Susan , Driessen Ann , Yashiro Hiroaki , Pors Susanne , Worm Andersen Maja , Feigh Michael , Yunis Carla , Bedossa Pierre , Stewart Michelle , Cater Heather L. , Wells Sara , Schattenberg Jörn M. , Anstee Quentin M. ,   The LITMUS Investigators, Anstee Quentin M. , Daly Ann K. , Cockell Simon , Tiniakos Dina , Bedossa Pierre , Burt Alastair , Oakley Fiona , Cordell Heather J. , Day Christopher P. , Wonders Kristy , Missier Paolo , McTeer Matthew , Vale Luke , Oluboyede Yemi , Breckons Matt , Boyle Jo , Bossuyt Patrick M. , Zafarmand Hadi , Vali Yasaman , Lee Jenny , Nieuwdorp Max , Holleboom Adriaan G. , Angelakis Athanasios , Verheij Joanne , Ratziu Vlad , Clément Karine , Patino-Navarrete Rafael , Pais Raluca , Paradis Valerie , Schuppan Detlef , Schattenberg Jörn M. , Surabattula Rambabu , Myneni Sudha , Kim Yong Ook , Straub Beate K. , Vidal-Puig Antonio , Vacca Michele , Rodrigues-Cuenca Sergio , Allison Mike , Kamzolas Ioannis , Petsalaki Evangelia , Campbell Mark , Lelliott Chris J. , Davies Susan , Orešič Matej , Hyötyläinen Tuulia , McGlinchey Aidan , Mato Jose M. , Millet Óscar , Dufour Jean-François , Berzigotti Annalisa , Masoodi Mojgan , Lange Naomi F. , Pavlides Michael , Harrison Stephen , Neubauer Stefan , Cobbold Jeremy , Mozes Ferenc , Akhtar Salma , Olodo-Atitebi Seliat , Banerjee Rajarshi , Shumbayawonda Elizabeth , Dennis Andrea , Andersson Anneli , Wigley Ioan , Romero-Gómez Manuel , Gómez-González Emilio , Ampuero Javier , Castell Javier , Gallego-Durán Rocío , Fernández-Lizaranzu Isabel , Montero-Vallejo Rocío , Karsdal Morten , Rasmussen Daniel Guldager Kring , Leeming Diana Julie , Sinisi Antonia , Musa Kishwar , Sandt Estelle , Tonini Maria Manuela , Bugianesi Elisabetta , Rosso Chiara , Armandi Angelo , Marra Fabio , Gastaldelli Amalia , Svegliati Gianluca , Boursier Jérôme , Francque Sven , Vonghia Luisa , Verrijken An , Dirinck Eveline , Driessen Ann , Ekstedt Mattias , Kechagias Stergios , Yki-Järvinen Hannele , Porthan Kimmo , Arola Johanna , van Mil Saskia , Papatheodoridis George , Cortez-Pinto Helena , Silva Ana Paula , Rodrigues Cecilia M. P. , Valenti Luca , Pelusi Serena , Petta Salvatore , Pennisi Grazia , Miele Luca , Liguori Antonio , Geier Andreas , Rau Monika , Trautwein Christian , Reißing Johanna , Aithal Guruprasad P. , Francis Susan , Palaniyappan Naaventhan , Bradley Christopher , Hockings Paul , Schneider Moritz , Newsome Philip N. , Hübscher Stefan , Wenn David , Magnanensi Jeremy , Trylesinski Aldo , Mayo Rebeca , Alonso Cristina , Duffin Kevin , Perfield James W. , Chen Yu , Hartman Mark L. , Yunis Carla , Miller Melissa , Chen Yan , McLeod Euan James , Ross Trenton , Bernardo Barbara , Schölch Corinna , Ertle Judith , Younes Ramy , Coxson Harvey , Simon Eric , Gogain Joseph , Ostroff Rachel , Alexander Leigh , Biegel Hannah , Kjær Mette Skalshøi , Harder Lea Mørch , Al-Sari Naba , Veidal Sanne Skovgård , Oldenburger Anouk , Ellegaard Jens , Balp Maria-Magdalena , Jennings Lori , Martic Miljen , Löffler Jürgen , Applegate Douglas , Torstenson Richard , Lindén Daniel , Fournier-Poizat Céline , Llorca Anne , Kalutkiewicz Michael , Pepin Kay , Ehman Richard , Horan Gerald , Ho Gideon , Tai Dean , Chng Elaine , Xiao Teng , Patterson Scott D. , Billin Andrew , Doward Lynda , Twiss James , Thakker Paresh , Derdak Zoltan , Yashiro Hiroaki , Landgren Henrik , Lackner Carolin , Gouw Annette , Hytiroglou Prodromos , Govaere Olivier , Brass Clifford , Tiniakos Dina , Perfield James W. , Petsalaki Evangelia , Davidsen Peter , Vidal-Puig Antonio 
Published: June 2024

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.