High-saturate-fat diet delays initiation of diethylnitrosamine-induced hepatocellular carcinoma.
High-saturate-fat diet delays initiation of diethylnitrosamine-induced hepatocellular carcinoma.
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高饱和脂肪饮食延迟二乙基亚硝胺诱导的肝细胞癌的发生
DOI：
10.1186/s12876-014-0195-9
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发表时间：
2014-11-20
影响因子：
2.4
通讯作者：
Qiao L
中科院分区：
文献类型：
--
作者：
Duan XY;Pan Q;Yan SY;Ding WJ;Fan JG;Qiao L
背景非酒精性脂肪性肝病（NAFLD）是肝细胞癌（HCC）的危险因素，但高脂饮食（HFD）与HCC之间的关系尚不完全清楚。在这项研究中，我们探讨了是否高饱和脂肪饮食影响肝癌诱导的二乙基亚硝胺（DEN）。方法成年SD大鼠随机分为以下组：正常饮食（NCD），HFD，NCD + DEN，和HFD + DEN。HFD含有2%胆固醇和10%猪油。在DEN治疗的小鼠中，通过灌胃给予致癌物质。分别在第10、12和14周结束时处死小鼠。HFD对肝癌发生的影响通过HCC发生率、肿瘤分化以及肿瘤结节的数量和大小来评估。Western blot和免疫组化检测增殖细胞核抗原（PCNA），酶联免疫吸附试验（ELISA）检测caspase-3，实时荧光定量PCR检测TNF-α和IL-6，进一步揭示了肝脏的增殖和凋亡特性。有趣的是，在10 - 14周期间，诱导高脂血症和肝脂肪变性的HFD减轻了HFD + DEN组中DEN相关的营养不良和纤维化进展。HFD + DEN组分化良好的HCC比例明显高于NCD + DEN组。HFD + DEN组肝癌结节数和平均体积也明显减少（P <0.01-0.05）。与NCD + DEN组相比，HFD + DEN组大鼠肝脏中PCNA、TNF-α、IL-6的表达和caspase-3的活化在第10周和第12周均受到抑制。
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.
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影响因子：
3.3
作者：
Grossmann, Michael E.;Mizuno, Nancy K.;Cleary, Margot P.
通讯作者：
Cleary, Margot P.
影响因子：
24
作者：
Jafri, Haseeb;Alsheikh-Ali, Alawi A.;Karas, Richard H.
通讯作者：
Karas, Richard H.
中国酒精性和非酒精性脂肪肝流行病学
影响因子：
4.1
作者：
Fan, Jian-Gao
通讯作者：
Fan, Jian-Gao
影响因子：
3.8
作者：
Khattab, Mahmoud A.;Eslam, Mohammed;Sharawe, Mohammed A.
通讯作者：
Sharawe, Mohammed A.
影响因子：
50.5
作者：
Strasak, A. M.;Pfeiffer, R. M.;Ulmer, H.
通讯作者：
Ulmer, H.