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

  1. Ghallab, Ahmed ORCID logo
  2. Myllys, Maiju ORCID logo
  3. Friebel, Adrian Robert ORCID logo
  4. Duda, Julia Christin ORCID logo
  5. Edlund, Karolina ORCID logo
  6. Halilbasic, Emina ORCID logo
  7. Vucur, Mihael
  8. Hobloss, Zaynab
  9. Brackhagen, Lisa
  10. Begher-Tibbe, Brigitte
  11. Hassan, Reham ORCID logo
  12. Burke, Michael ORCID logo
  13. Genç, Erhan
  14. Frohwein, Lynn Johann
  15. Hofmann, Ute ORCID logo
  16. Holland, Christian ORCID logo
  17. González, Daniela
  18. Keller, Magdalena
  19. Seddek, Abdel-Latif
  20. Abbas, Tahany
  21. Mohammed, Elsayed S. I.
  22. Teufel, Andreas
  23. Itzel, Timo
  24. Metzler, Sarah
  25. Marchan, Rosemarie ORCID logo
  26. Cadenas, Cristina ORCID logo
  27. Watzl, Carsten ORCID logo
  28. Nitsche, Michael ORCID logo
  29. Kappenberg, Franziska ORCID logo
  30. Luedde, Tom ORCID logo
  31. Longerich, Thomas ORCID logo
  32. Rahnenführer, Jörg ORCID logo
  33. Hoehme, Stefan ORCID logo
  34. Trauner, Michael ORCID logo
  35. Hengstler, Jan ORCID logo

Download
cells-10-02516-v2.pdf 7,41MB
WeightNameValue
1000 Titel
  • Spatio-Temporal Multiscale Analysis of Western Diet-Fed Mice Reveals a Translationally Relevant Sequence of Events during NAFLD Progression
1000 Autor/in
  1. Ghallab, Ahmed |
  2. Myllys, Maiju |
  3. Friebel, Adrian Robert |
  4. Duda, Julia Christin |
  5. Edlund, Karolina |
  6. Halilbasic, Emina |
  7. Vucur, Mihael |
  8. Hobloss, Zaynab |
  9. Brackhagen, Lisa |
  10. Begher-Tibbe, Brigitte |
  11. Hassan, Reham |
  12. Burke, Michael |
  13. Genç, Erhan |
  14. Frohwein, Lynn Johann |
  15. Hofmann, Ute |
  16. Holland, Christian |
  17. González, Daniela |
  18. Keller, Magdalena |
  19. Seddek, Abdel-Latif |
  20. Abbas, Tahany |
  21. Mohammed, Elsayed S. I. |
  22. Teufel, Andreas |
  23. Itzel, Timo |
  24. Metzler, Sarah |
  25. Marchan, Rosemarie |
  26. Cadenas, Cristina |
  27. Watzl, Carsten |
  28. Nitsche, Michael |
  29. Kappenberg, Franziska |
  30. Luedde, Tom |
  31. Longerich, Thomas |
  32. Rahnenführer, Jörg |
  33. Hoehme, Stefan |
  34. Trauner, Michael |
  35. Hengstler, Jan |
1000 Erscheinungsjahr 2021
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-09-23
1000 Erschienen in
1000 Quellenangabe
  • 10(10):2516
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.3390/cells10102516 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • 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.
1000 Sacherschließung
lokal non-invasive imaging
lokal transcriptomics
lokal intravital imaging
lokal NASH
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0003-0695-3403|https://orcid.org/0000-0001-9117-4572|https://orcid.org/0000-0002-9157-4418|https://orcid.org/0000-0002-3894-0124|https://orcid.org/0000-0002-0276-2143|https://orcid.org/0000-0002-4878-1470|https://frl.publisso.de/adhoc/uri/VnVjdXIsIE1paGFlbA==|https://frl.publisso.de/adhoc/uri/SG9ibG9zcywgWmF5bmFi|https://frl.publisso.de/adhoc/uri/QnJhY2toYWdlbiwgTGlzYQ==|https://frl.publisso.de/adhoc/uri/QmVnaGVyLVRpYmJlLCBCcmlnaXR0ZQ==|https://orcid.org/0000-0002-6569-7676|https://orcid.org/0000-0002-8516-9889|https://frl.publisso.de/adhoc/uri/R2Vuw6csIEVyaGFu|https://frl.publisso.de/adhoc/uri/RnJvaHdlaW4sIEx5bm4gSm9oYW5u|https://orcid.org/0000-0003-0823-9027|https://orcid.org/0000-0002-3060-5786|https://frl.publisso.de/adhoc/uri/R29uesOhbGV6LCBEYW5pZWxh|https://frl.publisso.de/adhoc/uri/S2VsbGVyLCBNYWdkYWxlbmE=|https://frl.publisso.de/adhoc/uri/U2VkZGVrLCBBYmRlbC1MYXRpZg==|https://frl.publisso.de/adhoc/uri/QWJiYXMsIFRhaGFueQ==|https://frl.publisso.de/adhoc/uri/TW9oYW1tZWQsIEVsc2F5ZWQgUy4gSS4=|https://frl.publisso.de/adhoc/uri/VGV1ZmVsLCBBbmRyZWFz|https://frl.publisso.de/adhoc/uri/SXR6ZWwsIFRpbW8=|https://frl.publisso.de/adhoc/uri/TWV0emxlciwgU2FyYWg=|https://orcid.org/0000-0003-4414-1633|https://orcid.org/0000-0003-3374-6418|https://orcid.org/0000-0001-5195-0995|https://orcid.org/0000-0002-2207-5965|https://orcid.org/0000-0001-8066-5333|https://orcid.org/0000-0002-6288-8821|https://orcid.org/0000-0001-8888-1030|https://orcid.org/0000-0002-8947-440X|https://orcid.org/0000-0002-9716-9587|https://orcid.org/0000-0002-1275-6425|https://orcid.org/0000-0002-1427-5246
1000 (Academic) Editor
1000 Label
1000 Förderer
  1. Deutsche Forschungsgemeinschaft |
  2. Bundesministerium für Bildung und Forschung |
  3. Austrian Science Fund |
  4. Robert Bosch Stiftung |
1000 Fördernummer
  1. GH 276/1-1 457840828; 427806116
  2. FKZ 031L0052; FKZ 031L0037
  3. F7310
  4. -
1000 Förderprogramm
  1. RTG 2624, Project P2
  2. Liver-LiSyM
  3. -
  4. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm RTG 2624, Project P2
    1000 Fördernummer GH 276/1-1 457840828; 427806116
  2. 1000 joinedFunding-child
    1000 Förderer Bundesministerium für Bildung und Forschung |
    1000 Förderprogramm Liver-LiSyM
    1000 Fördernummer FKZ 031L0052; FKZ 031L0037
  3. 1000 joinedFunding-child
    1000 Förderer Austrian Science Fund |
    1000 Förderprogramm -
    1000 Fördernummer F7310
  4. 1000 joinedFunding-child
    1000 Förderer Robert Bosch Stiftung |
    1000 Förderprogramm -
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6429790.rdf
1000 Erstellt am 2021-10-08T14:14:03.812+0200
1000 Erstellt von 254
1000 beschreibt frl:6429790
1000 Bearbeitet von 317
1000 Zuletzt bearbeitet Thu Oct 14 08:34:37 CEST 2021
1000 Objekt bearb. Wed Oct 13 12:25:12 CEST 2021
1000 Vgl. frl:6429790
1000 Oai Id
  1. oai:frl.publisso.de:frl:6429790 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

View source