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Human translatability of the GAN diet-induced obese mouse model of non-alcoholic steatohepatitis.
- Source :
-
BMC gastroenterology [BMC Gastroenterol] 2020 Jul 06; Vol. 20 (1), pp. 210. Date of Electronic Publication: 2020 Jul 06. - Publication Year :
- 2020
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Abstract
- Background: Animal models of non-alcoholic steatohepatitis (NASH) are important tools in preclinical research and drug discovery. Gubra-Amylin NASH (GAN) diet-induced obese (DIO) mice represent a model of fibrosing NASH. The present study directly assessed the clinical translatability of the model by head-to-head comparison of liver biopsy histological and transcriptome changes in GAN DIO-NASH mouse and human NASH patients.<br />Methods: C57Bl/6 J mice were fed chow or the GAN diet rich in saturated fat (40%), fructose (22%) and cholesterol (2%) for ≥38 weeks. Metabolic parameters as well as plasma and liver biomarkers were assessed. Liver biopsy histology and transcriptome signatures were compared to samples from human lean individuals and patients diagnosed with NASH.<br />Results: Liver lesions in GAN DIO-NASH mice showed similar morphological characteristics compared to the NASH patient validation set, including macrosteatosis, lobular inflammation, hepatocyte ballooning degeneration and periportal/perisinusoidal fibrosis. Histomorphometric analysis indicated comparable increases in markers of hepatic lipid accumulation, inflammation and collagen deposition in GAN DIO-NASH mice and NASH patient samples. Liver biopsies from GAN DIO-NASH mice and NASH patients showed comparable dynamics in several gene expression pathways involved in NASH pathogenesis. Consistent with the clinical features of NASH, GAN DIO-NASH mice demonstrated key components of the metabolic syndrome, including obesity and impaired glucose tolerance.<br />Conclusions: The GAN DIO-NASH mouse model demonstrates good clinical translatability with respect to the histopathological, transcriptional and metabolic aspects of the human disease, highlighting the suitability of the GAN DIO-NASH mouse model for identifying therapeutic targets and characterizing novel drug therapies for NASH.
Details
- Language :
- English
- ISSN :
- 1471-230X
- Volume :
- 20
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 32631250
- Full Text :
- https://doi.org/10.1186/s12876-020-01356-2