| First Author | Hu X | Year | 2020 |
| Journal | Carcinogenesis | Volume | 41 |
| Issue | 2 | Pages | 159-170 |
| PubMed ID | 31300810 | Mgi Jnum | J:288541 |
| Mgi Id | MGI:6416204 | Doi | 10.1093/carcin/bgz132 |
| Citation | Hu X, et al. (2020) A trans-fatty acid-rich diet promotes liver tumorigenesis in HCV core gene transgenic mice. Carcinogenesis 41(2):159-170 |
| abstractText | Excess consumption of trans-fatty acid (TFA), an unsaturated fatty acid containing trans double bonds, is a major risk factor for cardiovascular disease and metabolic syndrome. However, little is known about the link between TFA and hepatocellular carcinoma (HCC) despite it being a frequent form of cancer in humans. In this study, the impact of excessive dietary TFA on hepatic tumorigenesis was assessed using hepatitis C virus (HCV) core gene transgenic mice that spontaneously developed HCC. Male transgenic mice were treated for 5 months with either a control diet or an isocaloric TFA-rich diet that replaced the majority of soybean oil with shortening. The prevalence of liver tumors was significantly higher in TFA-rich diet-fed transgenic mice compared with control diet-fed transgenic mice. The TFA-rich diet significantly increased the expression of pro-inflammatory cytokines, as well as oxidative and endoplasmic reticulum stress, and activated nuclear factor-kappa B (NF-kappaB) and nuclear factor erythroid 2-related factor 2 (NRF2), leading to high p62/sequestosome 1 (SQSTM1) expression. Furthermore, the TFA diet activated extracellular signal-regulated kinase (ERK) and stimulated the Wnt/beta-catenin signaling pathway, synergistically upregulating cyclin D1 and c-Myc, driving cell proliferation. Excess TFA intake also promoted fibrogenesis and ductular reaction, presumably contributing to accelerated liver tumorigenesis. In conclusion, these results demonstrate that a TFA-rich diet promotes hepatic tumorigenesis, mainly due to persistent activation of NF-kappaB and NRF2-p62/SQSTM1 signaling, ERK and Wnt/beta-catenin pathways and fibrogenesis. Therefore, HCV-infected patients should avoid a TFA-rich diet to prevent liver tumor development. |
