Dietary Broccoli Lessens Development of Fatty Liver and Liver Cancer in Mice Given Diethylnitrosamine and Fed a Western or Control Diet

Abstract

Background: The high-fat and high-sugar Westernized diet that is popular worldwide is associated with increased body fat accumulation, which has been related to the development of nonalcoholic fatty liver disease (NAFLD). Without treatment, NAFLD may progress to hepatocellular carcinoma (HCC), a cancer with a high mortality rate. The consumption of broccoli in the United States has greatly increased in the last 2 decades. Epidemiologic studies show that incorporating brassica vegetables into the daily diet lowers the risk of several cancers, although, to our knowledge, this is the first study to evaluate HCC prevention through dietary broccoli.

Objective: We aimed to determine the impact of dietary broccoli on hepatic lipid metabolism and the progression of NAFLD to HCC. Our hypothesis was that broccoli decreases both hepatic lipidosis and the development of HCC in a mouse model of Western diet-enhanced liver cancer.

Methods: Adult 5-wk-old male B6C3F1 mice received a control diet (AIN-93M) or a Western diet (high in lard and sucrose, 19% and 31%, wt:wt, respectively), with or without freeze-dried broccoli (10%, wt:wt). Starting the following week, mice were treated once per week with diethylnitrosamine (DEN; 45 mg/kg body weight intraperitoneally at ages 6, 7, 8, 10, 11, and 12 wk). Hepatic gene expression, lipidosis, and tumor outcomes were analyzed 6 mo later, when mice were 9 mo old.

Results: Mice receiving broccoli exhibited lower hepatic triglycerides (P < 0.001) and NAFLD scores (P < 0.0001), decreased plasma alanine aminotransferase (P < 0.0001), suppressed activation of hepatic CD68(+) macrophages (P < 0.0001), and slowed initiation and progression of hepatic neoplasm. Hepatic Cd36 was downregulated by broccoli feeding (P = 0.006), whereas microsomal triglyceride transfer protein was upregulated (P = 0.045), supporting the finding that dietary broccoli decreased hepatic triglycerides.

Conclusion: Long-term consumption of whole broccoli countered both NAFLD development enhanced by a Western diet and hepatic tumorigenesis induced by DEN in male B6C3F1 mice.

Keywords: NAFLD; Western diet; broccoli; diethylnitrosamine; liver cancer.

FIGURE 1

Effect of DEN, broccoli, and a WD on plasma ALT in male B6C3F1 mice. Data are means ± SDs; n = 6–11. Means with different letters are statistically significant, P < 0.05. ALT, alanine aminotransferase; CON, control; DEN, diethylnitrosamine; WD, Western diet.

FIGURE 2

Effect of DEN, broccoli, and a WD on liver histologic alteration in lipodosis in male B6C3F1 mice. Liver sections were stained with hematoxylin and eosin. Representative images from each group are shown as 40× (large image) and 100× (small image) magnifications. TG vacuoles are indicated by arrows. CON, control; CV, central vein; DEN, diethylnitrosamine; PV, portal vein; WD, Western diet.

FIGURE 3

Effect of broccoli and a WD on ACC (A) and MTTP (B) in male B6C3F1 mice. Data are shown as fold change from the S-NB-CON group and are means ± SDs; n = 6. Means with different letters are statistically significant, P < 0.05. ACC, acetyl-CoA carboxylase; B, broccoli; CON, control; MTTP, microsomal triglyceride transfer protein; NB, no broccoli; S, saline; WD, Western diet.