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| Status |
Public on Jan 16, 2024 |
| Title |
Dietary intervention reverses molecular signatures of hepatocellular senescence in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
We applied RNA sequencing (RNA-seq) to study the effects of dietary intervention on hallmarks of NASH and molecular signatures of hepatocellular senescence in the Gubra-Amylin NASH (GAN) diet-induced obese (DIO) mouse model of NASH. GAN DIO-NASH mice with liver biopsy-confirmed NASH and fibrosis received dietary intervention by switching to chow feeding (chow reversal) for 8, 16, or 24 weeks. Untreated GAN DIO-NASH mice and chow-fed C57BL/6J mice served as controls.
We find that chow reversal promoted substantial benefits on metabolic, biochemical and histological outcomes accompanied by marked suppression of gene expression markers of hepatocellular senescence in GAN DIO-NASH mice. These therapeutic benefits were reflected by progressive clearance of senescent hepatocellular cells, making the model suitable for profiling potential senotherapeutics in preclinical drug discovery for NASH.
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| Overall design |
RNA-seq of poly A-enriched RNA isolated from GAN DIO-NASH mice or chow-reversal sampled at 8 weeks (n = 7), 16 weeks (n = 8), and 24 weeks (n = 8). Untreated GAN DIO-NASH mice at 8 weeks (n = 9), 16 weeks (n = 8), and 24 weeks (n = 7), and chow-fed C57BL/6J mice served as controls (24 weeks, n = 8)
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| Contributor(s) |
Madsen MR, Rørbeck EA |
| Citation(s) |
38308212 |
| Submission date |
Oct 26, 2023 |
| Last update date |
Feb 14, 2024 |
| Contact name |
Henrik Hansen |
| Organization name |
Gubra
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| Department |
Histology & NGS
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| Street address |
Hørsholm Kongevej 11
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| City |
Hørsholm |
| ZIP/Postal code |
2970 |
| Country |
Denmark |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (55)
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| GSM7866833 |
Liver, Vehicle 16 w, Rep 1 [16178] |
| GSM7866834 |
Liver, Chow-reversal 16 w, Rep 1 [16180] |
| GSM7866835 |
Liver, Vehicle 24 w, Rep 1 [16181] |
| GSM7866836 |
Liver, Chow-reversal 24 w, Rep 1 [16183] |
| GSM7866837 |
Liver, Chow Vehicle 24 w, Rep 2 [16184] |
| GSM7866838 |
Liver, Vehicle 8 w, Rep 2 [16185] |
| GSM7866839 |
Liver, Chow-reversal 8 w, Rep 2 [16187] |
| GSM7866840 |
Liver, Vehicle 16 w, Rep 2 [16188] |
| GSM7866841 |
Liver, Chow-reversal 16 w, Rep 2 [16190] |
| GSM7866842 |
Liver, Chow-reversal 24 w, Rep 2 [16193] |
| GSM7866843 |
Liver, Chow Vehicle 24 w, Rep 3 [16194] |
| GSM7866844 |
Liver, Vehicle 8 w, Rep 3 [16195] |
| GSM7866845 |
Liver, Chow-reversal 8 w, Rep 3 [16197] |
| GSM7866846 |
Liver, Vehicle 16 w, Rep 3 [16198] |
| GSM7866847 |
Liver, Chow-reversal 16 w, Rep 3 [16200] |
| GSM7866848 |
Liver, Vehicle 24 w, Rep 2 [16201] |
| GSM7866849 |
Liver, Chow-reversal 24 w, Rep 3 [16203] |
| GSM7866850 |
Liver, Chow Vehicle 24 w, Rep 4 [16204] |
| GSM7866851 |
Liver, Vehicle 8 w, Rep 4 [16205] |
| GSM7866852 |
Liver, Chow-reversal 8 w, Rep 4 [16207] |
| GSM7866853 |
Liver, Vehicle 16 w, Rep 4 [16208] |
| GSM7866854 |
Liver, Chow-reversal 16 w, Rep 4 [16210] |
| GSM7866855 |
Liver, Vehicle 24 w, Rep 3 [16211] |
| GSM7866856 |
Liver, Chow-reversal 24 w, Rep 4 [16213] |
| GSM7866857 |
Liver, Chow Vehicle 24 w, Rep 5 [16214] |
| GSM7866858 |
Liver, Vehicle 8 w, Rep 5 [16215] |
| GSM7866859 |
Liver, Chow-reversal 8 w, Rep 5 [16217] |
| GSM7866860 |
Liver, Vehicle 16 w, Rep 5 [16218] |
| GSM7866861 |
Liver, Chow-reversal 16 w, Rep 5 [16220] |
| GSM7866862 |
Liver, Vehicle 24 w, Rep 4 [16221] |
| GSM7866863 |
Liver, Chow-reversal 24 w, Rep 5 [16223] |
| GSM7866864 |
Liver, Chow Vehicle 24 w, Rep 6 [16224] |
| GSM7866865 |
Liver, Vehicle 8 w, Rep 6 [16225] |
| GSM7866866 |
Liver, Vehicle 8 w, Rep 7 [16227] |
| GSM7866867 |
Liver, Vehicle 16 w, Rep 6 [16228] |
| GSM7866868 |
Liver, Chow-reversal 16 w, Rep 6 [16230] |
| GSM7866869 |
Liver, Vehicle 24 w, Rep 5 [16231] |
| GSM7866870 |
Liver, Chow-reversal 24 w, Rep 6 [16233] |
| GSM7866871 |
Liver, Chow Vehicle 24 w, Rep 7 [16234] |
| GSM7866872 |
Liver, Vehicle 8 w, Rep 8 [16235] |
| GSM7866873 |
Liver, Chow-reversal 8 w, Rep 6 [16237] |
| GSM7866874 |
Liver, Vehicle 16 w, Rep 7 [16238] |
| GSM7866875 |
Liver, Chow-reversal 16 w, Rep 7 [16240] |
| GSM7866876 |
Liver, Vehicle 24 w, Rep 6 [16241] |
| GSM7866877 |
Liver, Chow-reversal 24 w, Rep 7 [16243] |
| GSM7866878 |
Liver, Chow Vehicle 24 w, Rep 8 [16244] |
| GSM7866879 |
Liver, Vehicle 8 w, Rep 9 [16245] |
| GSM7866880 |
Liver, Chow-reversal 8 w, Rep 7 [16247] |
| GSM7866881 |
Liver, Vehicle 16 w, Rep 8 [16248] |
| GSM7866882 |
Liver, Chow-reversal 16 w, Rep 8 [16250] |
| GSM7866883 |
Liver, Vehicle 24 w, Rep 7 [16251] |
| GSM7866884 |
Liver, Chow-reversal 24 w, Rep 8 [16253] |
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| Relations |
| BioProject |
PRJNA1032545 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE246328_GAN-DIO-NASH-Senescence_counts.txt.gz |
1.9 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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