Effects of fructose on liver gene expression profile in DEN-induced HCC model.

Excessive fructose consumption causes fatty liver disease and steatohepatitis, conditions that elevate liver cancer risk. Although fructose was documented to cause metabolic abnormalities and microbial dysbiosis, whether and how it triggers liver tumorigenesis was unknown. We now describe a mouse model in which fructose acts as a carcinogen, giving rise to intestinal dysbiosis and translocation of inflammation-evoking microbial products that reach the liver via the portal circulation. These inflammatory stimuli initiate hepatocellular carcinogenesis. Genetic enhancement of epithelial barrier integrity and microbiota depletion with broad spectrum antibiotics prevent fructose-induced steatosis and liver cancer. Overall design: Using DEN-induced and MUP-uPA HCC mouse models we investigated effects of diets rich in corn starch or fructose on intestinal barrier integrity, NASH development and hepatocarcinogenesis.