An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD).
Por:
Vacca M, Kamzolas I, Harder LM, Oakley F, Trautwein C, Hatting M, Ross T, Bernardo B, Oldenburger A, Hjuler ST, Ksiazek I, Lindén D, Schuppan D, Rodriguez-Cuenca S, Tonini MM, Castañeda TR, Kannt A, Rodrigues CMP, Cockell S, Govaere O, Daly AK, Allison M, Honnens de Lichtenberg K, Kim YO, Lindblom A, Oldham S, Andréasson AC, Schlerman F, Marioneaux J, Sanyal A, Afonso MB, Younes R, Amano Y, Friedman SL, Wang S, Bhattacharya D, Simon E, Paradis V, Burt A, Grypari IM, Davies S, Driessen A, Yashiro H, Pors S, Worm Andersen M, Feigh M, Yunis C, Bedossa P, Stewart M, Cater HL, Wells S, Schattenberg JM, Anstee QM, LITMUS Investigators, Tiniakos D, Perfield JW, Petsalaki E, Davidsen P and Vidal-Puig A
Publicada:
1 jun 2024
Resumen:
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.
Filiaciones:
Vacca M:
TVP Lab, WT/MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy.
Laboratory of Liver Metabolism and MASLD, Roger Williams Institute of Hepatology, London, UK.
Kamzolas I:
TVP Lab, WT/MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, UK
Harder LM:
Research and Early Development, Novo Nordisk A/S, Måløv, Copenhagen, Denmark
Oakley F:
Newcastle Fibrosis Research Group, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
Trautwein C:
Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
Hatting M:
Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
Ross T:
Internal Medicine research Research Unit, Pfizer Worldwide Research and Development, Cambridge, MA, USA
Bernardo B:
Internal Medicine research Research Unit, Pfizer Worldwide Research and Development, Cambridge, MA, USA
Oldenburger A:
CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany
Hjuler ST:
Research and Early Development, Novo Nordisk A/S, Måløv, Copenhagen, Denmark
Ksiazek I:
Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland
Lindén D:
Bioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism (CVRM), AstraZeneca BioPharmaceuticals R&D, Gothenburg, Sweden
Division of Endocrinology, Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Schuppan D:
Institute of Translational Immunology and Research Center for Immunotherapy, Johannes Gutenberg University Medical Center, Mainz, Germany
Rodriguez-Cuenca S:
TVP Lab, WT/MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
Tonini MM:
Luxembourg Institute of Health, Translational Medicine Operations Hub, Dudelange, Luxembourg
Castañeda TR:
R&D Diabetes & Portfolio Innovation and Excellence, Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, Frankfurt, Germany
Kannt A:
R&D Diabetes, Sanofi-Aventis Deutschland GmbH, Industriepark Hoechst, Frankfurt, Germany
Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Fraunhofer Innovation Center TheraNova and Goethe University, Frankfurt, Germany
Rodrigues CMP:
Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
Cockell S:
Bioinformatics Support Unit, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
Govaere O:
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
Daly AK:
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
Allison M:
Liver Unit, Cambridge University Hospitals NHS Foundation Trust & Cambridge NIHR Biomedical Research Centre, Cambridge, UK
Honnens de Lichtenberg K:
Research and Early Development, Novo Nordisk A/S, Måløv, Copenhagen, Denmark
Kim YO:
Institute of Translational Immunology and Research Center for Immunotherapy, Johannes Gutenberg University Medical Center, Mainz, Germany
Lindblom A:
Bioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism (CVRM), AstraZeneca BioPharmaceuticals R&D, Gothenburg, Sweden
Oldham S:
Bioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism (CVRM), AstraZeneca BioPharmaceuticals R&D, Gaithersburg, MD, USA
Andréasson AC:
Bioscience Cardiovascular, Research and Early Development Cardiovascular, Renal and Metabolism (CVRM), AstraZeneca BioPharmaceuticals R&D, Gothenburg, Sweden
Schlerman F:
Inflammation and Immunology Research Unit, Pfizer Worldwide Research and Development, Cambridge, MA, USA
Marioneaux J:
Fleur De Lis Holdings 10201 Dakins Dr. Richmond, Richmond, VA, USA
Sanyal A:
Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
Afonso MB:
Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
Younes R:
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
Amano Y:
Research, Takeda Pharmaceutical Company Limited, Fujisawa, Japan
Friedman SL:
Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Wang S:
Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Bhattacharya D:
Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Simon E:
Global Computational Biology and Digital Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany
Paradis V:
Department of Imaging and Pathology, Université Paris Diderot and Hôpital Beaujon, Paris, France
Burt A:
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK
Grypari IM:
Department of Pathology, Aretaeion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
Davies S:
Department of Cellular Pathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
Driessen A:
Department of Pathology, Antwerp University Hospital, Edegem, Belgium
Department of Molecular Imaging, Pathology, Radiotherapy, Oncology. Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium
Yashiro H:
Research, Takeda Pharmaceuticals Company Limited, Cambridge, MA, USA
Pors S:
Gubra, Hoersholm, Denmark
Worm Andersen M:
Gubra, Hoersholm, Denmark
Feigh M:
Gubra, Hoersholm, Denmark
Yunis C:
Pfizer, Inc
Internal Medicine and Hospital, Pfizer Research and Development, Lake Mary, FL, USA
Bedossa P:
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
LiverPat, Paris, France
Stewart M:
Mary Lyon Centre, MRC Harwell, Harwell Campus, Oxford, UK
Cater HL:
Mary Lyon Centre, MRC Harwell, Harwell Campus, Oxford, UK
Wells S:
Mary Lyon Centre, MRC Harwell, Harwell Campus, Oxford, UK
Schattenberg JM:
Department of Internal Medicine II, Saarland University Medical Centre, Homburg, Germany
Anstee QM:
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK
Tiniakos D:
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Department of Pathology, Aretaeion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Perfield JW:
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
Petsalaki E:
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, UK.
Davidsen P:
Research and Early Development, Novo Nordisk A/S, Måløv, Copenhagen, Denmark.
Ferring Pharmaceuticals A/S, International PharmaScience Center, Copenhagen, Denmark.
:
TVP Lab, WT/MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Centro de Investigación Príncipe Felipe, Valencia, Spain.
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