Troglitazone prevented the development of fatty liver under obese and diabetic condition in Otsuka Long-Evans Tokushima fatty rats

We aimed to clarify the effects of troglitazone to prevent the development of fatty liver in Otsuka Long-Evans Tokushima fatty (OLETF) rats, an obese type2 diabetes model. Treatment of 0.2% troglitazone for 16 weeks significantly decreased blood glucose, serum insulin and free fatty acid (FFA) concentration (P＜0.05 for each) in the OLETF rats leaving their food intake, body weight and general fat pad weight unaffected compared with those of their lean littermates, Long-Evans Tokushima Otsuka (LETO) rats. Troglitazone restored increase in liver weight and hepatic triglyceride(TG) content of the OLETF rats (P＜0.05 for each). These findings were accertained by histological examination which showed that fat deposition, necrosis and vacuolization of hepatocyte, markers for fatty liver, were diminished by troglitazone treatment. Messenger RNA expression of microsomal triglyceride transfer protein in the liver, a marker for hepatic TG output, was not significantly different between OLETF and LETO rats with or without troglitazone treatment. Fatty acid composition such as C18∶1(oleic acid) showed no remarkable change after troglitazone treatment in OLETF rats, indicating no dietary influence to hepatic lipogenesis. These indicate that reduction in circulating FFA level may be one of the main mechanisms for troglitazone to prevent the development of insulin resistance and fatty liver.