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Incorporation of a Survivable Liver Biopsy Procedure in Mice to Assess Non-alcoholic Steatohepatitis (NASH) Resolution
Published on: April 16, 2019
Interstrain differences in susceptibility to non-alcoholic steatohepatitis
Yuichi Yamazaki1, Satoru Kakizaki, Daichi Takizawa
1Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Journal of Gastroenterology and Hepatology
|September 18, 2007
Summary
Mice strains show different susceptibility to non-alcoholic steatohepatitis (NASH). C57BL/6N mice developed more severe NASH than C3H/HeN mice on a methionine- and choline-deficient diet, indicating interstrain differences in disease development.
Area of Science:
- Hepatology
- Gastroenterology
- Animal Models of Disease
Background:
- Non-alcoholic steatohepatitis (NASH) pathogenesis is not fully understood.
- Susceptibility to NASH varies across species and sexes.
- Investigating interstrain differences may elucidate NASH mechanisms.
Purpose of the Study:
- To investigate interstrain differences in NASH development.
- To utilize a dietary rodent model for NASH research.
- To identify molecular pathways contributing to NASH susceptibility.
Main Methods:
- Established a NASH model in C57BL/6N and C3H/HeN mice using a methionine- and choline-deficient (MCD) diet.
- Assessed liver injury markers, including serum alanine aminotransferase and inflammatory cell infiltration.
- Quantified hepatic steatosis, lipid peroxidation, and fibrosis using biochemical and histological methods.
Main Results:
- C57BL/6N mice exhibited significantly higher NASH severity, characterized by elevated liver enzymes, steatosis, lipid peroxidation, and fibrosis compared to C3H/HeN mice.
- Downregulation of beta-oxidation (CPT1A) and ketogenesis (mCS) mRNA was observed in C57BL/6N mice.
- No significant differences in MTP or SREBP1 expression were found between the strains.
Conclusions:
- Significant interstrain differences in NASH susceptibility were observed in the rodent dietary model.
- These findings highlight the importance of genetic background in NASH development.
- Further research into the molecular mechanisms underlying these interstrain differences could offer insights into human NASH pathophysiology.
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