A saturated fatty acid-rich diet enhances hepatic lipogenesis and tumorigenesis in HCV core gene transgenic mice.
A saturated fatty acid-rich diet enhances hepatic lipogenesis and tumorigenesis in HCV core gene transgenic mice.
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DOI：
10.1016/j.jnutbio.2020.108460
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发表时间：
2020-11
期刊：
影响因子：
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通讯作者：
Tanaka N
中科院分区：
文献类型：
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作者：
Diao P;Wang X;Jia F;Kimura T;Hu X;Shirotori S;Nakamura I;Sato Y;Nakayama J;Moriya K;Koike K;Gonzalez FJ;Aoyama T;Tanaka N
先前的研究表明，大量摄入饱和脂肪酸（SFA）是肝癌的危险因素。然而，目前尚不清楚饮食中的 SFA 如何影响肝脏肿瘤的发生。本研究旨在利用丙型肝炎病毒核心基因转基因 (HCVcpTg) 小鼠，研究富含 SFA 的饮食对肝脏肿瘤发生的影响，这些小鼠随着年龄的增长自发出现肝脂肪变性和肿瘤。用纯化的对照饮食或用氢化椰子油代替对照饮食中的大豆油制备的富含SFA的饮食治疗雄性HCVcpTg小鼠15个月，并评估表型变化。在这种特殊饮食中，几乎所有膳食脂肪酸都是SFA。长期喂养 HCVcpTg 小鼠富含 SFA 的饮食会增加肝脂肪变性、肝功能障碍和肝肿瘤的患病率，这可能是由于刺激从头脂肪生成、激活促炎和促癌转录因子核因子 -κB (NF-κB)、增强 c-Jun N 末端激酶/激活蛋白 1 (JNK/AP-1) 致癌基因细胞周期蛋白 D1 和 p62/sequestosome 1 的信号传导和诱导。富含 SFA 的饮食不会影响肝纤维化或自噬。总的来说，长期摄入富含SFA的饮食主要通过激活脂肪生成、NF-κB和JNK/AP-1信号传导促进肝脏肿瘤发生。因此，我们建议HCV感染者应避免过量摄入富含SFA的食物，以预防肝癌。
Previous studies suggested that high consumption of saturated fatty acid (SFA) is a risk factor for liver cancer. However, it remains unclear how dietary SFA affects liver tumorigenesis. This study aimed to investigate the impact of a SFA-rich diet on hepatic tumorigenesis using hepatitis C virus core gene transgenic (HCVcpTg) mice that spontaneously developed hepatic steatosis and tumors with aging. Male HCVcpTg mice were treated for 15 months with a purified control diet or SFA-rich diet prepared by replacing soybean oil in the control diet with hydrogenated coconut oil, and phenotypic changes were assessed. In this special diet, almost all dietary fatty acids were SFA. Long-term feeding of SFA-rich diet to HCVcpTg mice increased hepatic steatosis, liver dysfunction, and the prevalence of liver tumors, likely due to stimulation of de novo lipogenesis, activation of the pro-inflammatory and pro-oncogenic transcription factor nuclear factor-kappa B (NF-κB), enhanced c-Jun N-terminal kinase/activator protein 1 (JNK/AP-1) signaling and induction of the oncogenes cyclin D1 and p62/sequestosome 1. The SFA-rich diet did not affect liver fibrosis or autophagy. Collectively, long-term SFA-rich diet consumption promoted hepatic tumorigenesis mainly through activation of lipogenesis, NF-κB, and JNK/AP-1 signaling. We therefore propose that HCV-infected patients should avoid excessive intake of SFA-rich foods to prevent liver cancer.