Differential effects of a high fat or high carbohydrate diet on the onset of liver cancer in HBx TG mice

Abstract

Little is known about the impact of dietary factors on the progression of liver cancer. Thus, the goal of this study was to determine the liver-related consequences of long-term diet-induced obesity on the onset of hepatocellular carcinoma among different disease phases in the HBx TG mouse

model of hepatocellular carcinoma. To investigate the tumorigenic effect of a high fat (HFD) or high carbohydrate diet (HCD) in HBx TG mouse livers, mice were fed a high fat or high carbohydrate diet for 28, 36, or 40 weeks and age-matched mice were sacrificed at 12 months old, after the diet challenge. Hepatic steatosis was apparent and serum alanine aminotransferase and aspartate aminotransferase levels were significantly increased in HFD or HCD-fed HBx TG mice compared to mice fed regular chow. AKT and ERK showed greater activation in the HCD group compared to HFD and regular chow-fed groups. Together, these data indicated that chronic HCD consumption can produce more severe liver damage in HBx TG mice, which can potentially accelerate the onset of tumorigenesis by upregulating pERK-mediated ER stress. Consumption of excess fats or carbohydrates induced biochemical and pathological changes that could worsen the HCC. Food intake imbalance alone may not be sufficient to cause HCC, but it may be a risk factor that impairs liver cells functions and fosters tumor occurrence. Thus, diet may be an important and potentially modifiable determinant of liver cancer.