An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD)
Michèle Vacca; Ioannis Kamzolas; Lea Mørch Harder; Fiona Oakley; Christian Trautwein; Maximilian Hatting; Trenton T. Ross; Barbara Bernardo; Anouk Oldenburger; Sara Toftegaard Hjuler; Iwona Ksiazek; Daniel Lindén; Detlef Schuppan; Sergio Rodríguez‐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 J. Sanyal; Marta B. Afonso; Ramy Younes; Yuichiro Amano; Scott L. Friedman; Shuang Wang; Dipankar Bhattacharya; Eric J. Simon; Valérie Paradis; Alastair D. Burt; Ioanna Maria Grypari; Susan Davies; Ann Driessen; Hiroaki Yashiro; Susanne Elisabeth Pors; M Andersen; Michael Feigh; Carla Yunis; Pierre Bédossa; Michelle Stewart; Heather Cater; Sara Wells; Jörn M. Schattenberg; Quentin M. Anstee; The LITMUS Investigators; Quentin M. Anstee; Ann K. Daly; Simon Cockell; Dina Tiniakos; Pierre Bédossa; Alastair D. 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 Patiño‐Navarrete; Raluca Pais; Valérie Paradis; Detlef Schuppan; Jörn M. Schattenberg; Rambabu Surabattula; Sudha Rani Myneni; Yong Ook Kim; Beate K. Straub; Antonio Vidal-Puig; Michèle Vacca; Sergio Rodrigues-Cuenca; Mike Allison; Ioannis Kamzolas; Evangelia Petsalaki; Mark Campbell; Chris Lelliott; Susan Davies; Matej Orešič; Tuulia Hyötyläinen
This systematic review retrospectively evaluated murine preclinical models of MASLD across metabolic phenotype, histopathology, and transcriptomic similarity to human disease, developing an unbiased 'human proximity score' to rank model translatability. Western diet-induced models showed closest alignment with human MASH pathology and required extended duration and/or genetic modification to achieve significant fibrosis, whereas choline-deficient models rapidly induced advanced liver damage but poorly recapitulated human disease features. The ranking provides evidence-based guidance for selection of appropriate preclinical models to advance MASLD drug discovery and mechanistic research.
Regional applicability
The findings are applicable to UK-based preclinical MASLD research and drug development programmes, offering guidance on model selection to improve translational success rates. However, the review focused on murine models and does not directly address dietary or lifestyle intervention effectiveness in human UK populations.
Key measures
Human proximity score (unbiased ranking system); metabolic phenotype assessment; liver histopathology (steatosis, inflammation, fibrosis staging); transcriptome benchmarking against human MASLD tissue; MASH-fibrosis development rate and severity
Outcomes reported
The study ranked commonly used murine models of metabolic dysfunction-associated steatotic liver disease (MASLD) according to their proximity to human disease phenotype, measured through metabolic phenotyping, liver histopathology, and transcriptomic benchmarking against human samples. The ranking identifies Western diet models as most translationally relevant whilst choline-deficient models, despite rapid fibrosis induction, showed poor human alignment.
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