The genetic background shapes the susceptibility to mitochondrial dysfunction and NASH progression.
J Exp Med
; 220(4)2023 04 03.
Article
in En
| MEDLINE
| ID: mdl-36787127
ABSTRACT
Non-alcoholic steatohepatitis (NASH) is a global health concern without treatment. The challenge in finding effective therapies is due to the lack of good mouse models and the complexity of the disease, characterized by gene-environment interactions. We tested the susceptibility of seven mouse strains to develop NASH. The severity of the clinical phenotypes observed varied widely across strains. PWK/PhJ mice were the most prone to develop hepatic inflammation and the only strain to progress to NASH with extensive fibrosis, while CAST/EiJ mice were completely resistant. Levels of mitochondrial transcripts and proteins as well as mitochondrial function were robustly reduced specifically in the liver of PWK/PhJ mice, suggesting a central role of mitochondrial dysfunction in NASH progression. Importantly, the NASH gene expression profile of PWK/PhJ mice had the highest overlap with the human NASH signature. Our study exposes the limitations of using a single mouse genetic background in metabolic studies and describes a novel NASH mouse model with features of the human NASH.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Non-alcoholic Fatty Liver Disease
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
J Exp Med
Year:
2023
Document type:
Article
Affiliation country:
Switzerland