Enhancement of Carcinogenesis and Fatty Infiltration in the Pancreas in N-Nitrosobis(2-Oxopropyl) Amine-Treated Hamsters by High-Fat Diet
Enhancement of Carcinogenesis and Fatty Infiltration in the Pancreas in N-Nitrosobis(2-Oxopropyl) Amine-Treated Hamsters by High-Fat Diet
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DOI：
10.1097/mpa.0b013e318220e742
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发表时间：
2011-11-01
期刊：
影响因子：
2.9
通讯作者：
Takahashi, Mami
中科院分区：
文献类型：
--
作者：
Hori, Mika;Kitahashi, Tsukasa;Takahashi, Mami
目的：肥胖与胰腺癌风险增加相关，尽管其机制尚未详细阐明。本研究旨在阐明肥胖和高脂血症对胰腺癌的促进作用。方法：用N-亚硝基双(2-氧代丙基)胺(BOP)治疗六周龄雌性叙利亚金仓鼠，1周后饲喂高脂饮食(HFD)或标准饮食(STD)，持续6周或17周。结果：HFD组的体重以及血清脂质和瘦素水平显着高于STD组。 14周龄。胰腺导管腺癌仅发生在 BOP + HFD 组，14 周龄时的发生率为 67%（P < 0.01）。此外，25周龄时BOP+HFD组的多重性是BOP+STD组的2倍（P<0.05）。 BOP 治疗增加了胰腺脂肪浸润，HFD 进一步增强了胰腺脂肪浸润，这与 BOP 诱导的胰腺导管腺癌的进展以及胰腺中脂肪细胞因子和细胞增殖相关基因的表达上调相关。 结论：高脂饮食会增加血清脂质水平，增强胰腺脂肪浸润，并导致脂肪细胞因子产生异常，从而可能加速和增强胰腺癌。
Objectives: Obesity is associated with increased pancreatic cancer risk, although the mechanisms have yet to be detailed. This study aimed to elucidate promotion of pancreatic cancer by obesity and hyperlipidemia.Methods: Six-week-old female Syrian golden hamsters were treated with N-nitrosobis(2-oxopropyl) amine (BOP) and after 1 week were fed a high-fat diet (HFD) or standard diet (STD) for 6 or 17 weeks.Results: Body weight and serum levels of lipids and leptin were significantly higher in the HFD than the STD group at 14 weeks of age. Pancreatic ductal adenocarcinomas developed only in the BOP + HFD group, with an incidence of 67% (P < 0.01) at 14 weeks of age. In addition, the multiplicity was 2-fold greater in the BOP + HFD group than in the BOP + STD group (P < 0.05) at 25 weeks of age. Pancreatic fatty infiltration was increased by BOP treatment and further enhanced by the HFD, correlating with progression of BOP-induced pancreatic ductal adenocarcinoma and up-regulated expression of adipocytokines and cell proliferation-related genes in the pancreas.Conclusions: High-fat diet is shown to increase serum lipid levels and enhance fatty infiltration in the pancreas with abnormal adipocytokine production, which may accelerate and enhance pancreatic cancer.