@article{Roglans_Baena_Sangüesa_Velázquez_Griñán-Ferré_Pallàs_Sánchez_Alegret_Laguna-Egea_2021, title={Chronic liquid fructose supplementation does not cause liver tumorigenesis but elicits clear sex differences in the metabolic response in Sprague–Dawley rats}, volume={65}, url={https://foodandnutritionresearch.net/index.php/fnr/article/view/7670}, DOI={10.29219/fnr.v65.7670}, abstractNote={<p><strong><em>Background</em>:</strong>&nbsp;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 modifiable risk factors for NAFLD/HCC (e.g. hyper caloric diets rich in fructose) is essential.</p> <p><strong><em>Objective and design</em>:</strong>&nbsp;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 (RVT) in the last 4 months of treatment.</p> <p><strong><em>Results and discussion</em>:</strong>&nbsp;Rat livers showed no&nbsp;<em>de visu</em>&nbsp;or histological evidence of liver tumorigenesis. However, we observed metabolic abnormalities that could be related to cancer development mainly in the female fructose-supplemented rats, such as increases in weight, adiposity and hepatic triglyceride levels, as well as hyperglycaemia, hyperuricemia, hyperleptinemia and a reduced insulin sensitivity index, which were partially reversed by RVT. Therefore, we performed a targeted analysis of 84 cancer-related genes in the female liver samples, which revealed expression changes associated with cancer-related pathways. Analysis of individual genes indicated that some changes increased the risk of hepatocarcinogenesis (<em>Sfrp2</em>,&nbsp;<em>Ccl5</em>,&nbsp;<em>Socs3</em>, and&nbsp;<em>Gstp1</em>), while others exerted a protective/preventive effect (<em>Bcl2</em>&nbsp;and&nbsp;<em>Cdh1</em>).</p> <p><strong><em>Conclusion</em>:</strong>&nbsp;Our data clearly demonstrate that chronic fructose supplementation, as the sole dietary intervention, does not cause HCC development in rats.</p&gt;}, journal={Food & Nutrition Research}, author={Roglans Núria and Baena Miguel and Sangüesa Gemma and Velázquez Ana Magdalena and Griñán-Ferré Christian and Pallàs Mercè and Sánchez Rosa María and Alegret Marta and Laguna-Egea Juan Carlos}, year={2021}, month={Sep.} }