Abstract
BackgroundNonalcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC), but the association between a high-fat diet (HFD) and HCC is not fully understood. In this study, we investigated whether a high-saturate-fat diet affects hepatocarcinogenesis induced by administration of diethylnitrosamine (DEN).MethodsAdult SD rats were randomized into the following groups: normal chow diet (NCD), HFD, NCD + DEN, and HFD + DEN. The HFD contains 2% cholesterol and 10% lard oil. In mice with DEN treatment, the carcinogen was given via gavage. Mice were sacrificed at the end of 10, 12, and 14 weeks, respectively. The effects of HFD on hepatic carcinogenesis were assessed by HCC incidence, tumor differentiation, and the number and size of tumor nodules. Western blot and immunohistochemistry for proliferating cell nuclear antigen (PCNA), enzyme-linked immunosorbent assay (ELISA) for caspase-3, and real-time PCR for TNF-α and IL-6 further uncovered the proliferative and apoptotic properties of liver.ResultsIn contrast to the NCD group, DEN treatment (NCD + DEN group) led to hepatitis, cirrhosis, hepatic tumor, and decreased body weight. Interestingly, HFD, which induced hyperlipidemia and hepatic steatosis, attenuated DEN-related malnutrition and fibrosis progression in HFD + DEN group during 10–14 weeks. Moreover, the HFD + DEN group exhibited that the proportion of well differentiated HCC was much higher than that of NCD + DEN group. The number and average volume of HCC node were also significantly lowered in HFD + DEN group (P < 0.01-0.05). When compared to that of NCD + DEN group, there was an inhibited expression of PCNA, TNF-α, and IL-6, and activation of caspase-3 in the liver of HFD + DEN group at week 10 and 12.ConclusionsHFD restores malnutrition in the DEN-treated rats, which in turn inhibits the initiation of hepatic carcinogenesis and malignancy.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC), but the association between a high-fat diet (HFD) and HCC is not fully understood
Rats were allowed to acclimatize for a week on the normal chow diet (NCD) before grouping
In sharp contrast, when the rats fed on HFD were exposed to DEN (i.e., HFD + DEN group) for the same duration, there was a less reduction in body weight and BMI (P < 0.01, Table 1)
Summary
Nonalcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC), but the association between a high-fat diet (HFD) and HCC is not fully understood. HCC has clearly defined etiological factors such as chronic hepatitis B (CHB), chronic hepatitis C (CHC), long-term heavy alcohol consumption, exposure to aflatoxin, non-alcoholic steatohepatitis (NASH), some recent studies have interestingly suggested that HFD could delay the development of cancers in several organs such as breast, prostate, and liver [14,15,16,17,18,19]. To further support an anticancer effect of fatty acids, it has been shown that n-3 PUFA supplements possess antitumorigenic and anti-migratory abilities in breast and prostate cancers [15,16,17]. HFD (contains 13.6-23.5% fat) inhibits the density, average area, and unit area of HCC foci in F344 rats [19]
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