Abstract：
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.
摘要：
由于肥胖和代谢紊乱的患病率越来越高，全世界越来越多的患者被诊断为非酒精性脂肪性肝病和非酒精性脂肪性肝炎（NAFLD/NASH）。绝经后妇女的NAFLD发病率高于绝经前妇女。雌性激素水平的下降可能会对新陈代谢的恶化产生影响。在本研究中,我们研究了自发性糖尿病托里(SDT)脂肪大鼠作为NAFLD新动物模型的潜力。我们通过卵巢切除术（OVX）在雌性大鼠中创建了更年期模型。Sprague-Dawley(SD)大鼠,SDT大鼠,将SDT脂肪大鼠分为假手术组和OVX组，并维持至40周龄。结果表明，在SD和SDT大鼠中观察到OVX诱导的体重增加。此外,OVX诱导的肝甘油三酯积累在所有菌株中增加，与假SD大鼠相比，OVX-SDT脂肪大鼠的肝甘油三酯水平显着增加。此外，OVX-SDT脂肪大鼠肝纤维化恶化。此外,在SDT脂肪大鼠中观察到OVX诱导的血液ALT水平升高。基因表达分析表明，OVX诱导OVX大鼠Srebp1表达上调，Pemt和Mttp下调。这些结果表明，OVX-SDT脂肪大鼠表现出NASH与更严重的肝纤维化比未经治疗的动物，提示OVX诱导的雌激素减少可能增强肝脏中的脂质合成。也有可能,虽然是假设的，OVX可能减少VLDL分泌，这可能更强烈地诱导NASH。
