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

Abstract 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.