title: High-saturate-fat diet delays initiation of diethylnitrosamine-induced hepatocellular carcinoma.
abstract: BACKGROUND
  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. In this study, we investigated whether a high-saturate-fat diet affects hepatocarcinogenesis induced by administration of diethylnitrosamine (DEN).
  
  
  METHODS
  Adult 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  HFD restores malnutrition in the DEN-treated rats, which in turn inhibits the initiation of hepatic carcinogenesis and malignancy.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Duan
authors.forename: Qin
authors.initials: Q
authors.lastname: Pan
authors.forename: Shi-Yan
authors.initials: SY
authors.lastname: Yan
authors.forename: Wen-Jin
authors.initials: WJ
authors.lastname: Ding
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of medicine, Shanghai Key Laboratory of Children's Digestion and Nutrition, Shanghai 200092, China. fanjiangao@gmail.com.
authors.forename: Jian-Gao
authors.initials: JG
authors.lastname: Fan
authors.forename: Liang
authors.initials: L
authors.lastname: Qiao
mesh_terms: D000818:Animals; D017209:Apoptosis; D002273:Carcinogens; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D049109:Cell Proliferation; D059305:Diet, High-Fat / Q000009:adverse effects; D004052:Diethylnitrosamine; D005234:Fatty Liver / Q000209:etiology; D005355:Fibrosis; D006949:Hyperlipidemias / Q000209:etiology; D015850:Interleukin-6 / Q000032:analysis; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009752:Nutritional Status; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D002273:Carcinogens; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D004052:Diethylnitrosamine