Evidence map›Paper›PMID 34685496›Full record

ArticleCells2021

Spatio-Temporal Multiscale Analysis of Western Diet-Fed Mice Reveals a Translationally Relevant Sequence of Events during NAFLD Progression.

Ahmed Ghallab, Maiju Myllys, Adrian Friebel, Julia Duda, Karolina Edlund, Emina Halilbasic, Mihael Vucur, Zaynab Hobloss, Lisa Brackhagen, Brigitte Begher-Tibbe and 25 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
4.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 39 citations in OpenAlex.

  1. Identification of Changes in Gene Expression.Biometrical journal. Biometrische Zeitschrift · 2026
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  7. AlertGS: determining alerts for gene sets.Bioinformatics (Oxford, England) · 2025
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  18. Zonated quantification of immunohistochemistry in normal and steatotic livers.Virchows Archiv : an international journal of pathology · 2023
    Article
  19. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

35 authors at 8 institutions in 3 countries.

Ahmed GhallabLeibniz Research Centre for Working Environment and Human Factors, Department of Toxicology, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.ORCID 0000-0003-0695-3403
Maiju MyllysLeibniz Research Centre for Working Environment and Human Factors, Department of Toxicology, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.ORCID 0000-0001-9117-4572
Adrian FriebelInstitute of Computer Science & Saxonian Incubator for Clinical Research (SIKT), University of Leipzig, Haertelstr. 16-18, 04107 Leipzig, Germany.
Julia DudaDepartment of Statistics, TU Dortmund University, 44227 Dortmund, Germany.ORCID 0000-0002-3894-0124
Karolina EdlundLeibniz Research Centre for Working Environment and Human Factors, Department of Toxicology, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.ORCID 0000-0002-0276-2143
Emina HalilbasicHans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria.ORCID 0000-0002-4878-1470
Mihael VucurDepartment of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty at Heinrich-Heine-University, University Hospital Duesseldorf, 40225 Dusseldorf, Germany.
Zaynab HoblossLeibniz Research Centre for Working Environment and Human Factors, Department of Toxicology, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.
Lisa BrackhagenLeibniz Research Centre for Working Environment and Human Factors, Department of Toxicology, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.
Brigitte Begher-TibbeLeibniz Research Centre for Working Environment and Human Factors, Department of Toxicology, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.
Reham HassanLeibniz Research Centre for Working Environment and Human Factors, Department of Toxicology, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.ORCID 0000-0002-6569-7676
Michael BurkeMRI Unit, Leibniz Research Centre for Working Environment and Human Factors, Department of Psychology and Neurosciences, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.ORCID 0000-0002-8516-9889
Erhan GencMRI Unit, Leibniz Research Centre for Working Environment and Human Factors, Department of Psychology and Neurosciences, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.
Lynn Johann FrohweinSiemens Healthcare GmbH, 91052 Erlangen, Germany.
Ute HofmannDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, University of Tübingen, Auerbachstr. 112, 70376 Stuttgart, Germany.ORCID 0000-0003-0823-9027
Christian H HollandInstitute of Computational Biomedicine, Heidelberg University, Faculty of Medicine, Bioquant-Im Neuenheimer Feld 267, 69120 Heidelberg, Germany.ORCID 0000-0002-3060-5786
Daniela GonzálezLeibniz Research Centre for Working Environment and Human Factors, Department of Toxicology, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.
Magdalena KellerLeibniz Research Centre for Working Environment and Human Factors, Department of Toxicology, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.
Abdel-Latif SeddekDepartment of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, South Valley University, Qena 83523, Egypt.
Tahany AbbasHistology Department, Faculty of Medicine, South Valley University, Qena 83523, Egypt.
Elsayed S I MohammedDepartment of Histology and Cytology, Faculty of Veterinary Medicine, South Valley University, Qena 83523, Egypt.
Andreas TeufelDepartment of Medicine I, University Hospital, 93053 Regensburg, Germany.
Timo ItzelDepartment of Medicine I, University Hospital, 93053 Regensburg, Germany.
Sarah MetzlerLeibniz Research Centre for Working Environment and Human Factors, Department of Immunology, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.
Rosemarie MarchanLeibniz Research Centre for Working Environment and Human Factors, Department of Toxicology, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.
Cristina CadenasLeibniz Research Centre for Working Environment and Human Factors, Department of Toxicology, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.
Carsten WatzlLeibniz Research Centre for Working Environment and Human Factors, Department of Immunology, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.ORCID 0000-0001-5195-0995
Michael A NitscheLeibniz Research Centre for Working Environment and Human Factors, Department of Psychology and Neurosciences, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.
Franziska KappenbergDepartment of Statistics, TU Dortmund University, 44227 Dortmund, Germany.
Tom LueddeDepartment of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty at Heinrich-Heine-University, University Hospital Duesseldorf, 40225 Dusseldorf, Germany.
Thomas LongerichTranslational Gastrointestinal Pathology, Institute of Pathology, University Hospital Heidelberg, D-69120 Heidelberg, Germany.ORCID 0000-0001-8888-1030
Jörg RahnenführerDepartment of Statistics, TU Dortmund University, 44227 Dortmund, Germany.
Stefan HoehmeInstitute of Computer Science & Saxonian Incubator for Clinical Research (SIKT), University of Leipzig, Haertelstr. 16-18, 04107 Leipzig, Germany.ORCID 0000-0002-9716-9587
Michael TraunerHans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria.ORCID 0000-0002-1275-6425
Jan G HengstlerLeibniz Research Centre for Working Environment and Human Factors, Department of Toxicology, Technical University Dortmund, Ardeystr. 67, 44139 Dortmund, Germany.
TU Dortmund University · DESouth Valley University · EGDüsseldorf University Hospital · DEHeidelberg University · DEMedical University of Vienna · ATUniversity Hospital Regensburg · DEDr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology · DESiemens Healthineers (Germany) · DE

Funding

Austrian Science Fund F7310Bundesministerium für Bildung und Forschung LiSyM grant FKZ 031L0037Bundesministerium für Bildung und Forschung the Liver-LiSyM grant FKZ 031L0052Deutsche Forschungsgemeinschaft GH 276/1-1; project no. 457840828Deutsche Forschungsgemeinschaft RTG 2624 "Biostatistical Methods for High-Dimensional Data in Toxicologythe Robert Bosch Stiftung, Stuttgart Stuttgart
6 · The paper itself

Abstract

Mouse models of non-alcoholic fatty liver disease (NAFLD) are required to define therapeutic targets, but detailed time-resolved studies to establish a sequence of events are lacking. Here, we fed male C57Bl/6N mice a Western or standard diet over 48 weeks. Multiscale time-resolved characterization was performed using RNA-seq, histopathology, immunohistochemistry, intravital imaging, and blood chemistry; the results were compared to human disease. Acetaminophen toxicity and ammonia metabolism were additionally analyzed as functional readouts. We identified a sequence of eight key events: formation of lipid droplets; inflammatory foci; lipogranulomas; zonal reorganization; cell death and replacement proliferation; ductular reaction; fibrogenesis; and hepatocellular cancer. Functional changes included resistance to acetaminophen and altered nitrogen metabolism. The transcriptomic landscape was characterized by two large clusters of monotonously increasing or decreasing genes, and a smaller number of 'rest-and-jump genes' that initially remained unaltered but became differentially expressed only at week 12 or later. Approximately 30% of the genes altered in human NAFLD are also altered in the present mouse model and an increasing overlap with genes altered in human HCC occurred at weeks 30-48. In conclusion, the observed sequence of events recapitulates many features of human disease and offers a basis for the identification of therapeutic targets.

Indexed as

AnimalsCarcinoma, HepatocellularDiet, WesternDisease Models, AnimalDisease ProgressionLiverLiver NeoplasmsMiceMice, Inbred C57BLNon-alcoholic Fatty Liver Diseaseintravital imagingNASHnon-invasive imagingtranscriptomics

Identifiers

PMID34685496
PMCPMC8533774
OpenAlexW3199019000

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.