Dietary broccoli impedes Western diet-enhanced fatty liver and hepatocellular carcinoma development

Liver is the metabolic center for energy homeostasis in our body, maintaining a balance between carbohydrate and fat metabolism. The “Westernized” dietary pattern, which is known for high saturated fat and refined sugar and rooted in the lifestyle of a large proportion of the world’s population, may greatly disrupt energy balance, resulting in obesity and obesity-related diseases. Non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma, which is also a possible endpoint of NAFLD, are both enhanced by adiposity and inflammation, and almost symptomless until serious damage is caused in liver. However, these diseases can be preventable, by changing lifestyle and diet. Broccoli, a well-accepted brassica vegetable in the United States, has the potential to reduce cancer risk and ameliorate inflammation. Therefore, in this study, we aimed to understand the impact of dietary broccoli on the development of NAFLD and liver cancer in mice fed a Western diet. Accordingly, we proposed a whole dietary broccoli intervention. A combined Western diet-fed and diethylnitrosamine (DEN)-treated mouse liver cancer models was used in order to evaluate the changes in hepatic lipidosis, macrophage activation, and tumorigenesis after long-term consumption of broccoli. Our results show that dietary broccoli decreased hepatic lipidosis as early as 3 months after initiation, and effectively down-regulated liver damage. The enlarged hepatic triglyceride pool due to the Western diet was narrowed by dietary broccoli, lowering the influx of non-esterified fatty acids but increasing the excretion of very-low-density lipoprotein. Activation of hepatic macrophages, was lowered by continues consumption of broccoli. Furthermore, DEN-induced liver tumor size and hepatic neoplasm-related lesion formation were both decreased by dietary broccoli. In addition, as an incidental finding, intraperitoneal DEN-induced nasal epithelial neoplasm-related lesions in B6C3F1 mice are first reported in this study. Overall, whole broccoli dietary intervention has the potential to impede the progression of NAFLD, from hepatic steatosis, through steatohepatitis, to hepatocellular carcinoma. This study fills gaps of knowledge about the impact of broccoli on hepatic lipid metabolism, supports the cancer preventive effect of brassicas revealed by epidemiologic studies, and further encourages the whole food dietary intervention. Translation to clinical studies is needed