Chronic liquid fructose supplementation does not cause liver tumorigenesis but elicits clear sex differences in the metabolic response in Sprague–Dawley rats

  • Núria Roglans Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; Institute of Biomedicine, University of Barcelona, Barcelona, Spain; and Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn), Madrid, Spain
  • Miguel Baena Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain
  • Gemma Sangüesa Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain
  • Ana Magdalena Velázquez Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; and Institute of Biomedicine, University of Barcelona, Barcelona, Spain
  • Christian Griñán-Ferré Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; and Institute of Neuroscience (UBNeuro), University of Barcelona, Barcelona, Spain
  • Mercè Pallàs Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; and Institute of Neuroscience (UBNeuro), University of Barcelona, Barcelona, Spain
  • Rosa María Sánchez Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; Institute of Biomedicine, University of Barcelona, Barcelona, Spain; and Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn), Madrid, Spain
  • Marta Alegret Department of Pharmacology, Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain; Institute of Biomedicine, University of Barcelona, Barcelona, Spain; and Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn), Madrid, Spain
  • Juan Carlos Laguna-Egea University of Barcelona
DOI: https://doi.org/10.29219/fnr.v65.7670
Keywords: diethyl nitrosamine, hepatocellular cancer, metabolic syndrome, sugar-sweetened beverages, sugary drinks

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.

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Published
2021-09-22
How to Cite
Roglans N., Baena M., Sangüesa G., Velázquez A. M., Griñán-Ferré C., Pallàs M., Sánchez R. M., Alegret M., & Laguna-Egea J. C. (2021). Chronic liquid fructose supplementation does not cause liver tumorigenesis but elicits clear sex differences in the metabolic response in Sprague–Dawley rats. Food & Nutrition Research, 65. https://doi.org/10.29219/fnr.v65.7670
Issue
Vol 65 (2021)
Section
Original Articles
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