An increasing number of patients worldwide are being diagnosed with
nonalcoholic fatty liver disease and
nonalcoholic steatohepatitis (
NAFLD/NASH) because of the growing prevalence of
obesity and metabolic disorders. The incidence of
NAFLD is higher in postmenopausal women than in premenopausal women. The decline in the level of female
hormones might have an effect on the deterioration of metabolism. In the present study, we investigated the potential of Spontaneously Diabetic Torii (SDT) fatty rats as a new animal model for
NAFLD. We created a menopausal model by
ovariectomy (OVX) in female rats. Sprague-Dawley (SD) rats, SDT rats, and SDT-fatty rats were divided into
sham and OVX groups and maintained until 40 weeks of age. The results showed that OVX-induced
weight gain was observed in SD and SDT rats. In addition, OVX-induced hepatic
triglyceride accumulation was increased in all strains, and there was a significant increase in hepatic
triglyceride levels in OVX-SDT fatty rats compared to those in
Sham-SD rats. Furthermore,
liver fibrosis was worsened in the OVX-SDT fatty rats. In addition, OVX-induced increase in blood ALT level was observed in SDT-fatty rats. Gene expression analysis showed OVX-induced upregulation of Srebp1 expression and downregulation of Pemt and
Mttp in OVX rats. These results indicate that OVX-SDT fatty rats exhibit NASH with more severe hepatic
fibrosis than untreated animals, suggesting that OVX-induced
estrogen reduction may have enhanced
lipid synthesis in the liver. It is also possible, although hypothetical, that OVX may decrease VLDL secretion, which may more strongly induce NASH.