GEO series

A Mouse Model for Metabolic Dysfunction-associated Steatotic Liver Disease and Hepatocellular Carcinoma [RNA-seq]

GSE246221 Mus musculus; Homo sapiens Expression profiling by high throughput sequencing 148 samples Submitted 2024/06/17 Platform GPL24676Platform GPL24247

Summary

The lack of an appropriate preclinical model of metabolic dysfunction-associated steatotic liver disease (MASLD) that recapitulates the whole disease spectrum impedes exploration of disease pathophysiology and the development of effective treatment strategies. Considering the fact that MASLD patients accompanying type 2 diabetes mellitus (T2DM) have high risk of developing metabolic dysfunction-associated steatohepatitis (MASH), advanced fibrosis, and HCC, we treated low-dose streptozotocin (STZ; 40 mg/kg) for 5 consecutive days and subsequently fed a high-fat diet (HFD) to male C57BL/6J mice at 7 weeks of age (STZ+HFD). STZ+HFD mice gradually developed fatty liver, MASH, hepatic fibrosis, and hepatocellular carcinoma (HCC) in the context of metabolic dysfunction. In particular, from 20 weeks of age, MASH was evident, and from 32 weeks of age, advanced fibrosis was developed. At 38 weeks, a proportion of STZ+HFD mice developed HCC, which was subsequently observed in all mice up to 68 weeks of age. Furthermore, the hepatic transcriptomic features of STZ+HFD mice closely reflected those of obese patients with T2DM, MASH and MASLD-related HCC. Notably, dietary changes and tirzepatide administration alleviated MASH, hepatic fibrosis, and hepatic tumorigenesis in STZ+HFD mice. In conclusion, a murine model recapitulating the main histopathologic, transcriptomic, and metabolic alterations observed in MASLD patients with metabolic dysfunction was successfully established.

Published in

A male mouse model for metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma

Jeong BK, Choi WI, Choi W et al. · Nature communications 2024 · PMID 39090079 · doi:10.1038/s41467-024-50660-y

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Direct links to NCBI, no account and no request form: the whole study as GSE246221_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 148 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1032104 and SRA study SRP468408. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39090079) ↗

Study design

9 conditions, mostly with about 5 replicates each

STZ+HFD model, 56w, biological replication ×6 Healthy control,7w, biological replication ×5 STZ+HFD model, 14w, biological replication ×5 STZ+HFD model, 20w, biological replication ×5 STZ+HFD model, 32w, biological replication ×5 STZ+HFD model, 44w, biological replication ×5 STZ+HFD model, 50w, biological replication ×4 Acutre streptozotocin-treated state,8w, biolo… ×3 +1 more

Supports a case/control comparison: 5 samples read as cases, 5 as controls.

9 replicated groups read from the first 40 of 148 sample titles; they account for 40 of them. Check it against the sample list below before relying on it.

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