It has been reported that diet and nutrition play important roles in the occurrence and development of
hepatocellular carcinoma (HCC). In this study, we investigated the potential
tumor-promoting mechanisms of a high-fat diet (HFD) in mice with dietondiethylnitrosamine (DEN)-induced hepatocarcinogenesis. HFD significantly decreased the survival rate and induced severe
liver dysfunction in DEN-induced mice, as indicated by increased serum
glutamic-pyruvic transaminase (ALT), glutamic oxalacetic
transaminase (AST), and
alkaline phosphatase (ALP) levels and increased liver index, liver nodule count, and γ-glutamyltransferase (γ-GT) activity. Moreover, an increased number of fat droplets and HCCs were found in the livers of the HFD mice, who displayed little
collagen in and around the
liver cancer groove and the infiltration of large number of inflammatory cells, such as macrophages, compared with the control mice. HFD also significantly increased
proliferating cell nuclear antigen (
PCNA), nuclear factor-κB (NF-κB),
cyclin D1,
tumor necrosis factor (TNF), and
interleukin-1 (IL-1) expression levels in the liver. In vitro, we found that the
inducible nitric oxide synthase (iNOS) percentage increased in macrophages after
palmitic acid treatment, as well as the secretion of inflammatory factors and
cytokines such as interleukin-6(IL-6), interleukin-10(IL-10), CCL2,
Interferon γ (IFN-γ), and TNF. Thus, our results demonstrate that an HFD may promote DEN-induced hepatocarcinogenesis in mice by destroying liver function and enhancing the inflammatory response by recruiting and polarizing macrophages in the liver. This study could therefore provide new insights into the
tumor promoting effects of an HFD in HCC.