Chronic liquid fructose supplementation does not cause liver tumorigenesis but elicits clear sex differences in the metabolic response in Sprague–Dawley rats
Open Access
- 22 September 2021
- journal article
- research article
- Published by SNF Swedish Nutrition Foundation in Food & Nutrition Research
- Vol. 65, 1-15
- https://doi.org/10.29219/fnr.v65.7670
Abstract
Background: 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. Objective and design: 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. Results and discussion: Rat livers showed no de visu 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 (Sfrp2, Ccl5, Socs3, and Gstp1), while others exerted a protective/preventive effect (Bcl2 and Cdh1). Conclusion: Our data clearly demonstrate that chronic fructose supplementation, as the sole dietary intervention, does not cause HCC development in rats.Keywords
This publication has 40 references indexed in Scilit:
- Glycemic index, glycemic load, dietary carbohydrate, and dietary fiber intake and risk of liver and biliary tract cancers in Western EuropeansAnnals of Oncology, 2012
- Resveratrol Helps Recovery from Fatty Liver and Protects against Hepatocellular Carcinoma Induced by Hepatitis B Virus X Protein in a Mouse ModelCancer Prevention Research, 2012
- Liver AMP/ATP ratio and fructokinase expression are related to gender differences in AMPK activity and glucose intolerance in rats ingesting liquid fructoseThe Journal of Nutritional Biochemistry, 2011
- Effects of carbohydrates on satiety: differences between liquid and solid foodCurrent Opinion in Clinical Nutrition and Metabolic Care, 2011
- Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancerNature Communications, 2010
- Glycemic load in relation to hepatocellular carcinoma among patients with chronic hepatitis infectionAnnals of Oncology, 2009
- DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene listsNucleic Acids Research, 2007
- Regulation of glutathione transferase P: A tumor marker of hepatocarcinogenesisBiochemical and Biophysical Research Communications, 2007
- Sexual dimorphism in lipid metabolic phenotype associated with old age in Sprague–Dawley ratsExperimental Gerontology, 2004
- Different effect of simvastatin and atorvastatin on key enzymes involved in VLDL synthesis and catabolism in high fat/cholesterol fed rabbitsBritish Journal of Pharmacology, 1999