Dietary fructose promotes liver carcinogenesis by inducing the malignant transformation of hepatic progenitor cells. (July 2021)

• Record Type: Journal Article
• Authors: Hu, Qingqing; Ye, Jianghao; Zhu, Meng-Lu; Jin, Yuancheng; Yang, Xiaohui; Wu, Miaolian
• Is Part Of: Journal of functional foods. Volume 82(2021)
• Publication Date: 2021-07
• Subjects: Liver cancer -- Hepatic progenitor cells -- Diethylnitrosamine -- Fructose -- Dietary exposure; NAFLD nonalcoholic fatty liver disease -- NASH nonalcoholic steatohepatitis -- HCC hepatocellular carcinoma -- HPCs hepatic progenitors -- DEN diethylnitrosamine -- H&E hematoxylin–eosin -- GSTP1 glutathione S-transferase pi 1 -- EpCAM epithelial cell adhesion molecule -- IL-6 interleukin -- IFN-γ interferon-γ -- TNF-α tumor necrosis factor-α; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2021.104489
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: Dietary fructose promotes diethylnitrosamine-induced liver tumor initiation. Excessive dietary fructose induces steatotic hepatitis. Dietary fructose promotes the hepatic progenitor cell proliferation. Fructose enhances the tumor initiating capability of hepatic progenitor cells. Dietary fructose promotes the malignant transformation of hepatic progenitor cells. Abstract: The incidence of nonalcoholic fatty liver disease (NAFLD)-associated liver cancer is rising particularly in western societies. Dietary fructose has been increasingly reported as a significant contributor for the onset of NAFLD. However, the association between a high-fructose diet and liver cancer incidence is not fully understood. In this study, we investigated the effect of dietary fructose on liver tumorigenesis. In a mouse model of diethylnitrosamine (DEN)-induced liver tumor initiation, high-fructose diet was found to significantly increased hepatic lipid deposition and expression of inflammatory cytokines in mouse livers. Besides, DEN administration induced the malignant transformation of hepatic progenitor cells (HPCs) into malignant tumor initiating cells, while DEN + Fructose mice had significantly enriched HPCs with enhanced proliferation, invasion, chemoresistance, and tumorigenic capabilities. This study for the first time demonstrates that fructose promotes liver carcinogenesis via increasing tumorigenic HPCs and inflammatory microenvironment, which warrants precautionary control of the excessive intake of dietary fructose.