Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2015; 21(30): 9067-9078
Published online Aug 14, 2015. doi: 10.3748/wjg.v21.i30.9067
Female spontaneously diabetic Torii fatty rats develop nonalcoholic steatohepatitis-like hepatic lesions
Yukihito Ishii, Yu Motohashi, Makoto Muramatsu, Yoshiaki Katsuda, Katsuhiro Miyajima, Tomohiko Sasase, Takahisa Yamada, Tohru Matsui, Shinichi Kume, Takeshi Ohta
Yukihito Ishii, Makoto Muramatsu, Yoshiaki Katsuda, Tomohiko Sasase, Takeshi Ohta, Japan Tobacco Inc., Central Pharmaceutical Research Institute, Osaka 569-1125, Japan
Katsuhiro Miyajima, Japan Tobacco Inc., Central Pharmaceutical Research Institute, Toxicology Research Laboratories, Hadano, Kanagawa 257-0024, Japan
Takahisa Yamada, Niigata University, Graduate School of Science and Technology, Nishi-ku, Niigata 950-2181, Japan
Tohru Matsui, Shinichi Kume, Kyoto University, Graduate School of Agriculture, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan
Author contributions: Ishii Y, Motohashi Y and Ohta T designed the research; Muramatsu M, Sasase T, Katsuda Y and Sasase T performed the research and analyzed the data; Ohta T, Yamada T, Matsui T and Kume S edited the manuscript; Ishii Y and Motohashi Y wrote the paper.
Institutional review board statement: The study was reviewed and approved by Japan Tobacco Biological/Pharmacological Research Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Japan Tobacco Biological/Pharmacological Research Laboratories (IACUC protocol number: 00745).
Conflict-of-interest statement: We declare no conflicts of interest regarding this study.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yukihito Ishii, PhD, Japan Tobacco Inc., Central Pharmaceutical Research Institute, 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, Japan. yukihito.ishii@jt.com
Telephone: +81-72-6819700 Fax: +81-72-6819722
Received: December 25, 2014
Peer-review started: December 26, 2014
First decision: April 23, 2015
Revised: May 14, 2015
Accepted: June 9, 2015
Article in press: June 10, 2015
Published online: August 14, 2015
Abstract

AIM: To investigate the histological features of the liver in spontaneously diabetic Torii (SDT) fatty rats compared with age-matched Sprague-Dawley (SD) rats.

METHODS: Female SDT Leprfa (SDT fatty) rats and age-matched SD rats were fed ad libitum. Body weight and biochemical parameters, such as serum glucose, triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels as well as fatty acid and TG accumulation in the liver were evaluated at 8 wk of age in the non-fasting state and at 8-wk intervals from 8 to 40 wk of age. Histopathological examinations of the liver were performed using hematoxylin and eosin and Sirius Red staining as well as double staining for ED-1 and toluidine blue. The expression of genes involved in TG synthesis, inflammation, and fibrosis was examined in the liver.

RESULTS: SDT fatty rats showed significantly increased body weight compared with SD rats. Serum glucose, TG, and TC levels were significantly higher in SDT fatty rats compared with SD rats. The serum AST and ALT levels in SDT fatty rats were significantly elevated at 8 wk of age compared with the levels in SD rats. Hepatic TG content was marked in SDT fatty rats from 8 to 32 wk of age. Histopathologically, severe hepatosteatosis accompanied by inflammation was observed at 8 wk of age, and fibrosis started to occur at 32 wk of age. Furthermore, Sirius Red and ED-1 staining were increased in the liver at 32 wk of age. Hepatic gene expression related to TG synthesis, inflammation and fibrosis tended to increase in SDT fatty rats compared with SD rats, and the gene expression related to TG secretion was decreased in SDT fatty rats compared with SD rats.

CONCLUSION: Female SDT fatty rats have the potential to become an important animal model of nonalcoholic steatohepatitis with type 2 diabetes and obesity.

Keywords: Nonalcoholic steatohepatitis, Spontaneously diabetic Torii fatty rat, Fibrosis, Fatty liver, Metabolic syndrome

Core tip: Nonalcoholic steatohepatitis (NASH) is recognized as a major risk for progression to cirrhosis and liver failure or to hepatocellular carcinoma. In this study, we investigated the histological features of the liver in female spontaneously diabetic Torii (SDT) fatty rats. The SDT fatty rats exhibited pathophysiological features of NASH, and fibrosis appeared in the liver without dietary manipulation. Female SDT fatty rats have the potential to become an important animal model of NASH with type 2 diabetes and obesity, a condition for which few models currently exist.