Female spontaneously diabetic Torii fatty rats develop nonalcoholic steatohepatitis-like hepatic lesions.
OBJECTIVE
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 Lepr(fa) (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.


CONCLUSIONS
Female SDT fatty rats have the potential to become an important animal model of nonalcoholic steatohepatitis with type 2 diabetes and obesity.
Yukihito Ishii, Makoto Muramatsu, Yoshiaki Katsuda, Tomohiko Sasase, Takeshi Ohta, Japan Tobacco Inc., Central Pharmaceutical Research Institute, Osaka 569-1125, Japan.
Yukihito
Y
Ishii
Yukihito Ishii, Makoto Muramatsu, Yoshiaki Katsuda, Tomohiko Sasase, Takeshi Ohta, Japan Tobacco Inc., Central Pharmaceutical Research Institute, Osaka 569-1125, Japan.
Yu
Y
Motohashi
Yukihito Ishii, Makoto Muramatsu, Yoshiaki Katsuda, Tomohiko Sasase, Takeshi Ohta, Japan Tobacco Inc., Central Pharmaceutical Research Institute, Osaka 569-1125, Japan.
Makoto
M
Muramatsu
Yukihito Ishii, Makoto Muramatsu, Yoshiaki Katsuda, Tomohiko Sasase, Takeshi Ohta, Japan Tobacco Inc., Central Pharmaceutical Research Institute, Osaka 569-1125, Japan.
Yoshiaki
Y
Katsuda
Yukihito Ishii, Makoto Muramatsu, Yoshiaki Katsuda, Tomohiko Sasase, Takeshi Ohta, Japan Tobacco Inc., Central Pharmaceutical Research Institute, Osaka 569-1125, Japan.
Katsuhiro
K
Miyajima
Yukihito Ishii, Makoto Muramatsu, Yoshiaki Katsuda, Tomohiko Sasase, Takeshi Ohta, Japan Tobacco Inc., Central Pharmaceutical Research Institute, Osaka 569-1125, Japan.
Tomohiko
T
Sasase
Yukihito Ishii, Makoto Muramatsu, Yoshiaki Katsuda, Tomohiko Sasase, Takeshi Ohta, Japan Tobacco Inc., Central Pharmaceutical Research Institute, Osaka 569-1125, Japan.
Takahisa
T
Yamada
Yukihito Ishii, Makoto Muramatsu, Yoshiaki Katsuda, Tomohiko Sasase, Takeshi Ohta, Japan Tobacco Inc., Central Pharmaceutical Research Institute, Osaka 569-1125, Japan.
Tohru
T
Matsui
Yukihito Ishii, Makoto Muramatsu, Yoshiaki Katsuda, Tomohiko Sasase, Takeshi Ohta, Japan Tobacco Inc., Central Pharmaceutical Research Institute, Osaka 569-1125, Japan.
Shinichi
S
Kume
Yukihito Ishii, Makoto Muramatsu, Yoshiaki Katsuda, Tomohiko Sasase, Takeshi Ohta, Japan Tobacco Inc., Central Pharmaceutical Research Institute, Osaka 569-1125, Japan.
Takeshi
T
Ohta
D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D008055:Lipids / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000473:pathology; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D012737:Sex Factors; D013045:Species Specificity; D015430:Weight Gain
D015415:Biomarkers; D001786:Blood Glucose; D008055:Lipids; D012333:RNA, Messenger; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
Fatty liver; Fibrosis; Metabolic syndrome; Nonalcoholic steatohepatitis; Spontaneously diabetic Torii fatty rat