mRNA array in liver tissue samples of Sprague-Dawley rats

Non-alcoholic fatty liver disease (NAFLD) has increased over the last decades and may evolve into hepatocellular carcinoma (HCC). As HCC is challenging to treat, knowledge on the modifia-ble risk factors for NAFLD/HCC, (e.g. hypercaloric diets rich in fructose) is essential. We used a model of diethyl nitrosamine-induced hepatocarcinogenesis to investigate the liver cancer-promoting effects of a diet supplemented with 10% liquid fructose, administered to male and female rats for 11 months. A subset of the fructose-supplemented rats received resveratrol in the last 4 months of treatment. We observed metabolic abnormalities mainly in the female fructose-supplemented rats (increases in weight, adiposity, and plasma glucose and triglycerides, as well as liver triglycerides and a reduced insulin sensitivity index), which were partially reversed by resveratrol. The livers of fructose-supplemented rats showed no de visu or histological evi-dence of liver tumorigenesis. Targeted analysis of 84 cancer-related genes in the female liver samples revealed expression changes associated with cancer-related pathways, but individual genes indicated that some changes increased the risk of hepatocarcinogenesis (Sfrp2, Ccl5, Socs3, and Gstp1), while others exerted a protective/preventive effect (Bcl2 and Cdh1). In conclusion, our data do not clearly demonstrate that chronic fructose supplementation promotes HCC development in rats. The expression of 84 mature cancer mRNAs in the liver of Sprague-rats corresponding to the different syudy groups (Control CT, Fructose FRC and Fructose plus Resveratrol)