An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD)

被引：42

作者：

Vacca, Michele ^{[1
,2
,3
,56
]}

Kamzolas, Ioannis ^{[1
,4
,56
]}

Harder, Lea Morch ^{[5
,94
]}

Oakley, Fiona ^{[6
,51
]}

Trautwein, Christian ^{[7
,81
]}

Hatting, Maximilian ^{[7
]}

Ross, Trenton ^{[8
,91
]}

Bernardo, Barbara ^{[8
,91
]}

Oldenburger, Anouk ^{[9
,94
]}

Hjuler, Sara Toftegaard ^{[5
]}

Ksiazek, Iwona ^{[10
]}

Linden, Daniel ^{[11
,12
,97
]}

Schuppan, Detlef ^{[13
,14
,55
]}

Rodriguez-Cuenca, Sergio ^{[1
]}

Tonini, Maria Manuela ^{[15
,64
]}

Castaneda, Tamara R. ^{[16
]}

Kannt, Aimo ^{[17
,18
,19
]}

Rodrigues, Cecilia M. P. ^{[20
,76
]}

Cockell, Simon ^{[21
,51
]}

Govaere, Olivier ^{[22
,109
]}

Daly, Ann K. ^{[22
,51
]}

Allison, Michael ^{[23
,24
]}

de Lichtenberg, Kristian Honnens ^{[5
]}

Kim, Yong Ook ^{[13
,14
,55
]}

Lindblom, Anna ^{[11
]}

Oldham, Stephanie ^{[25
]}

Andreasson, Anne-Christine ^{[26
]}

Schlerman, Franklin ^{[27
]}

Marioneaux, Jonathon ^{[28
]}

Sanyal, Arun ^{[29
]}

Afonso, Marta B. ^{[20
]}

Younes, Ramy ^{[22
,30
,92
]}

Amano, Yuichiro ^{[31
]}

Friedman, Scott L. ^{[32
]}

Wang, Shuang ^{[32
]}

Bhattacharya, Dipankar ^{[32
]}

Simon, Eric ^{[33
,92
]}

Paradis, Valerie ^{[34
,35
,54
]}

Burt, Alastair ^{[22
,36
,51
]}

Grypari, Ioanna Maria ^{[37
]}

Davies, Susan ^{[38
,56
]}

Driessen, Ann ^{[39
,40
,70
]}

Yashiro, Hiroaki ^{[41
,104
]}

Pors, Susanne ^{[42
]}

Andersen, Maja Worm ^{[42
]}

Feigh, Michael ^{[42
]}

Yunis, Carla ^{[43
,44
,91
]}

Bedossa, Pierre ^{[22
,45
,51
]}

Stewart, Michelle ^{[46
]}

Cater, Heather L. ^{[46
]}

机构：

[1] Univ Cambridge, WT MRC Inst Metab Sci, TVP Lab, Cambridge, England

[2] Univ Bari Aldo Moro, Interdisciplinary Dept Med, Bari, Italy

[3] Roger Williams Inst Hepatol, Lab Liver Metab & MASLD, London, England

[4] European Bioinformat Inst EMBL EBI, European Mol Biol Lab, Wellcome Genome Campus, Cambridge, England

[5] Novo Nordisk AS, Res & Early Dev, Copenhagen, Denmark

[6] Newcastle Univ, Fac Med Sci, Newcastle Fibrosis Res Grp, Biosci Inst, Newcastle Upon Tyne, Tyne & Wear, England

[7] Univ Hosp RWTH Aachen, Dept Med 3, Aachen, Germany

[8] Pfizer Worldwide Res & Dev, Internal Med Res Res Unit, Cambridge, MA USA

[9] Boehringer Ingelheim Pharma GmbH & Co KG, CardioMetab Dis Res, Biberach, Germany

[10] Novartis Pharma AG, Novartis Inst BioMed Res, Basel, Switzerland

[11] AstraZeneca BioPharmaceut R&D, Biosci Metab, Res & Early Dev Cardiovasc Renal & Metab CVRM, Gothenburg, Sweden

[12] Univ Gothenburg, Sahlgrenska Acad, Dept Neurosci & Physiol, Div Endocrinol, Gothenburg, Sweden

[13] Johannes Gutenberg Univ Mainz, Med Ctr, Inst Translat Immunol, Mainz, Germany

[14] Johannes Gutenberg Univ Mainz, Med Ctr, Res Ctr Immunotherapy, Mainz, Germany

[15] Luxembourg Inst Hlth, Translat Med Operat Hub, Dudelange, Luxembourg

[16] Sanofi Aventis Deutschland GmbH, R&D Diabet & Portfolio Innovat & Excellence, Ind Pk Hoechst, Frankfurt, Germany

[17] Sanofi Aventis Deutschland GmbH, R&D Diabet, Ind Pk Hoechst, Frankfurt, Germany

[18] Fraunhofer Innovat Ctr TheraNova, Fraunhofer Inst Translat Med & Pharmacol ITMP, Frankfurt, Germany

[19] Goethe Univ, Frankfurt, Germany

[20] Univ Lisbon, Res Inst Med, Fac Pharm, Lisbon, Portugal

[21] Newcastle Univ, Bioinformat Support Unit, Fac Med Sci, Newcastle Upon Tyne, Tyne & Wear, England

[22] Newcastle Univ, Translat & Clin Res Inst, Fac Med Sci, Newcastle Upon Tyne, Tyne & Wear, England

[23] Cambridge Univ Hosp NHS Fdn Trust, Liver Unit, Cambridge, England

[24] Cambridge NIHR Biomed Res Ctr, Cambridge, England

[25] AstraZeneca BioPharmaceut R&D, Biosci Metab, Res & Early Dev Cardiovas Renal & Metab CVRM, Gaithersburg, MD USA

[26] AstraZeneca BioPharmaceut R&D, Biosci Cardiovasc, Res & Early Dev Cardiovasc Renal & Metab CVRM, Gothenburg, Sweden

[27] Pfizer Worldwide Res & Dev, Inflammat & Immunol Res Unit, Cambridge, MA USA

[28] Fleur De Lis Holdings, 10201 Dakins Dr Richmond, Richmond, VA USA

[29] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA USA

[30] Boehringer Ingelheim Int GmbH, Ingelheim, Germany

[31] Takeda Pharmaceut Co Ltd, Res, Fujisawa, Kanagawa, Japan

[32] Icahn Sch Med Mt Sinai, Div Liver Dis, New York, NY 10029 USA

[33] Boehringer Ingelheim Pharma GmbH & Co KG, Global Computat Biol & Digital Sci, Biberach, Germany

[34] Univ Paris Diderot, Dept Imaging & Pathol, Paris, France

[35] Hop Beaujon, Paris, France

[36] Newcastle Upon Tyne Hosp NHS Trust, Newcastle NIHR Biomed Res Ctr, Newcastle Upon Tyne, Tyne & Wear, England

[37] Natl & Kapodistrian Univ Athens, Aretaeion Hosp, Med Sch, Dept Pathol, Athens, Greece

[38] Cambridge Univ Hosp NHS Fdn Trust, Dept Cellular Pathol, Cambridge, England

[39] Antwerp Univ Hosp, Dept Pathol, Edegem, Belgium

[40] Univ Antwerp, Fac Med & Hlth Sci, Dept Mol Imaging, Pathol,Radiotherapy,Oncol, Antwerp, Belgium

[41] Takeda Pharmaceut Co Ltd, Res, Cambridge, MA USA

[42] Gubra, Horsholm, Denmark

[43] Pfizer Inc, Lake Mary, FL USA

[44] Pfizer Res & Dev, Internal Med & Hosp, Lake Mary, FL USA

[45] LiverPat, Paris, France

[46] MRC Harwell, Mary Lyon Ctr, Harwell Campus, Oxford, England

[47] Saarland Univ, Med Ctr, Dept Internal Med 2, Homburg, Germany

[48] Eli Lilly & Co, Lilly Res Lab, Indianapolis, IN 46285 USA

[49] Ctr Invest Principe Felipe, Valencia, Spain

[50] Ferring Pharmaceut AS, Int PharmaSci Ctr, Copenhagen, Denmark

来源：

NATURE METABOLISM | 2024年 / 6卷 / 06期

基金：

欧盟地平线“2020”; 英国医学研究理事会; 美国国家卫生研究院;

关键词：

HEPATIC STEATOSIS; SCORING SYSTEM; WESTERN DIET; MOUSE MODEL; WEIGHT-LOSS; PROGRESSION; MICE; ALGORITHM; DISCOVERY; STATEMENT;

D O I：

10.1038/s42255-024-01043-6

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1178 / +

页数：32

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