Female spontaneously diabetic Torii fatty rats develop nonalcoholic steatohepatitis-like hepatic lesions

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 nonfasting 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.

Elevated glucagon-like peptide-1 on a high-fat diet feeding prevents the incidence of diabetes mellitus in Spontaneously Diabetic Torii <i>Lepr^fa</i>rats

Nutritional regulation plays a critical role to reduce the incidence or progression of diabetes mellitus. In this study, we investigated the effects of a high-fat diet on Spontaneously Diabetic Torii Leprfa (SDT fatty) rats, a novel model for obese type 2 diabetes. The SDT fatty rats were divided into two dietary groups, which were fed a high-fat diet or a standard diet for 18 weeks, from 6 to 24 weeks of age. The calorie intake in the high-fat diet (HF) group was reduced after 10 weeks of age and the group inhibited an incidence of diabetes. Interestingly, the HF induced an increase of serum glucagon-like peptide-1 (GLP-1) levels in SDT fatty rats with refeeding. Fat tissue weights in the HF group increased, but the visceral fat/subcutaneous fat (V/S) ratio decreased. Moreover, histopathological observations revealed an improvement of the pancreatic abnormalities and fatty liver in the HF group. In conclusion, a preventive effect on diabetes in rats fed a high-fat diet has a relation with an increase in incretin hormone, and it might be advantageous for prevention of incidence or progression of diabetes to develop functional foods inducing an increase in incretin hormone.