mRNA array in liver tissue samples of Sprague-Dawley rats. 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. Overall design: 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)