Nonalcoholic steatohepatitis (NASH) is a progressive
liver disease, and some patients develop
hepatic cirrhosis/
carcinoma. Animal models play key roles in the development of new
therapies for NASH. In this study, the pharmacological effects of
metformin and
pioglitazone were investigated in female Spontaneously Diabetic Torii (SDT) fatty rats to verify the utility of this model. The anti-diabetic drugs were administered to SDT fatty rats fed a
cholesterol-enriched diet from 4 to 25 weeks, and changes in food intake,
body weight, and blood chemistry parameters were evaluated every 4 weeks. The hepatic
lipid content,
mRNA expression in relation to
lipid synthesis,
inflammation, and
fibrosis, and histopathological analyses were performed at 25 weeks.
Pioglitazone improved
hyperglycemia,
hyperlipidemia, and abnormalities in hepatic parameters. The
insulin levels were lower than those in the control rats before 16 weeks. Plasma
glucose levels in the
metformin-treated rats were lower than those in the control rats, and plasma
alanine aminotransferase levels temporarily decreased. The
lipid content and some
mRNA expression in relation to
fibrosis in the liver decreased with
pioglitazone treatment, and the
mRNA expression of
microsomal triglyceride transfer protein increased. Hepatic
fibrosis observed in the SDT fatty rats improved with
pioglitazone treatment; however, the effect with
metformin treatment was partial. These results in both drugs are in line with results in the human study, suggesting that the SDT fatty rat is useful for developing new anti-NASH drugs that show potential to regulate
glucose/lipid metabolism.