Research Papers:

Development of hepatocellular cancer induced by long term low fat-high carbohydrate diet in a NAFLD/NASH mouse model

Alessandra Tessitore _, Valentina Mastroiaco, Antonella Vetuschi, Roberta Sferra, Simona Pompili, Germana Cicciarelli, Remo Barnabei, Daria Capece, Francesca Zazzeroni, Carlo Capalbo and Edoardo Alesse

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Oncotarget. 2017; 8:53482-53494. https://doi.org/10.18632/oncotarget.18585

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Alessandra Tessitore1, Valentina Mastroiaco1, Antonella Vetuschi1, Roberta Sferra1, Simona Pompili1, Germana Cicciarelli1, Remo Barnabei2, Daria Capece1, Francesca Zazzeroni1, Carlo Capalbo3 and Edoardo Alesse1

1Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy

2S. Salvatore Hospital, Unit of Laboratory Medicine, 67100 L’Aquila, Italy

3Department of Molecular Medicine, University “La Sapienza”, 00161 Roma, Italy

Correspondence to:

Alessandra Tessitore, email: alessandra.tessitore@univaq.it

Keywords: NAFLD, NASH, hepatic cancer, LF-HC diet, HF diet

Received: December 12, 2016     Accepted: May 29, 2017     Published: June 21, 2017


Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease. It can progress to nonalcoholic steatohepatitis (NASH) and, in a percentage of cases, to hepatocarcinogenesis. The strong incidence in western countries of obesity and metabolic syndrome, whose NAFLD is the hepatic expression, is thought to be correlated to consumption of diets characterized by processed food and sweet beverages. Previous studies described high-fat diet-induced liver tumors. Conversely, the involvement of low-fat/high-carbohydrate diet in the progression of liver disease or cancer initiation has not been described yet. Here we show for the first time hepatic cancer formation in low-fat/high-carbohydrate diet fed NAFLD/NASH mouse model. Animals were long term high-fat, low-fat/high-carbohydrate or standard diet fed. We observed progressive liver damage in low-fat/high-carbohydrate and high-fat animals after 12 and, more, 18 months. Tumors were detected in 20% and 50% of high-fat diet fed mice after 12 and 18 months and, interestingly, in 30% of low-fat/high-carbohydrate fed animals after 18 months. No tumors were detected in standard diet fed mice. Global increase of hepatic interleukin-1β, interleukin-6, tumor necrosis factor-α and hepatocyte growth factor was detected in low-fat/high-carbohydrate and high-fat with respect to standard diet fed mice as well as in tumor with respect to non-tumor bearing mice. A panel of 15 microRNAs was analyzed: some of them revealed differential expression in low-fat/high-carbohydrate with respect to high-fat diet fed groups and in tumors. Data here shown provide the first evidence of the involvement of low-fat/high-carbohydrate diet in hepatic damage leading to tumorigenesis.

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