ID 112472
Author
Deuschle, Ulrich Phenex Pharmaceuticals AG
Taira, Shu Fukui Prefectural University
Nishida, Takeshi University of Toyama
Fujimoto, Makoto University of Toyama
Hijikata, Takao Musashino University
Keywords
TSOD mice
HCC
Tumor metabolism
Bile acid
Spontaneous tumorigenesis model
Content Type
Journal Article
Description
Background and aims Tsumura-Suzuki obese diabetic (TSOD) is a good model of metabolic syndrome showing typical lesions found in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, and develops spontaneous hepatic tumors with a high frequency. Majority of the developing tumors overexpress glutamine synthetase (GS), which is used as a marker of hepatocellular carcinoma (HCC). The aim of this study is to assess the status of expression of metabolism-related genes and the level of bile acids in the TSOD mice-derived tumors and to determine the association with metabolic dysregulation between human HCC and TSOD mice-derived tumors.
Methods GS-positive hepatic tumors or adjacent normal tissues from 71-week-old male TSOD mice were subjected to immunohistochemical staining (IHC), quantitative RT-PCR (qRT-PCR), quantitation of cholic acid and taurocolic acid.
Results We found that downregulation of the rate-limiting enzyme for betaine synthesis (BADH), at both mRNA and protein levels in GS-positive TSOD mice-derived tumors. Furthermore, the bile acid receptor FXR and the bile acid excretion pump BSEP (Abcb11) were found to be downregulated, whereas BAAT and Akr1c14, involved in primary bile acid synthesis and bile acid conjugation, were found to be upregulated at mRNA level in GS-positive TSOD mice-derived tumors. BAAT and Akr1c14 was also overexpressed at protein levels. Total cholic acid was found to be increased in GS-positive TSOD mice-derived tumors.
Conclusion Our results strongly support the significance of TSOD mice as a model of spontaneously developing HCC.
Journal Title
Hepatology International
ISSN
19360533
19360541
NCID
AA12728536
Publisher
Springer
Volume
12
Issue
3
Start Page
254
End Page
261
Published Date
2018-04-12
Rights
This is a post-peer-review, pre-copyedit version of an article published in Hepatology International. The final authenticated version is available online at: https://doi.org/10.1007/s12072-018-9860-3
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Author
departments
Medical Sciences