High-saturate-fat diet delays initiation of diethylnitrosamine-induced hepatocellular carcinoma

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.

A novel chemoprotective effect of tiopronin against diethylnitrosamine‐induced hepatocellular carcinoma in rats: Role of ASK1/P38 MAPK‐P53 signalling cascade

“…In this study, the induction of HCC was accompanied by a significant decrease in the total body weight and deterioration of the liver functions as well as an elevation of AFP tumour marker in the animals treated with DENA. These findings can be explained by the fact that, DENA is a well‐known genotoxic hepatocarcinogen which induce an energy‐wasting syndrome known as cancer cachexia . Additionally, our results showed that prolonged DENA administration caused a redox imbalance.…”

“…The liver function tests among control, DENA-and tiopronin + DENA-treated groups fact that, DENA is a well-known genotoxic hepatocarcinogen which induce an energy-wasting syndrome known as cancer cachexia. 38,39 Additionally, our results showed that prolonged DENA administration caused a redox imbalance. This was evidenced by a significant decrease in CAT and GPx activities, as well as increase of NO and MDA levels in animals treated with DENA.…”

The differential effects of low birth weight and Western diet consumption upon early life hepatic fibrosis development in guinea pig

“…mRNA expression was normalized to housekeeper GAPDH (Duan et al . ) and miR expression to miR‐let‐7a. There was no significant effect of either birth weight or diet on GAPDH mRNA or miR‐let‐7a expression.…”

Utilization of animal models to investigate nonalcoholic steatohepatitis-associated hepatocellular carcinoma

“…Co-implanted hepatoma cells with hepatic stellate cells (HSC) isolated from fatty liver promoted the growth of xenografts compared to those co-implanted with HSC from normal livers, which is attributed to the release of cytokines such as vascular endothelial growth factor (VEGF), interleukin-1α (IL-1α) and transforming growth factor-β (TGF-β) from in situ activated HSCs in fatty liver [71]. However, conflicting results were acquired in a different study [72], which claims that feeding rats with saturated fat diet for 10-12 weeks delayed the initiation of DEN-induced hepatic carcinogenesis. Apparently, these two studies had different focuses and experimental designs; therefore, more studies are needed to address emerging questions in better defined conditions.…”