Yin Xin, Li Yu-Sang, Ye Sha-Zhou, Zhang Ting, Zhang Yi-Wen, Xi Yang, Tang He-Bin
Lab of Hepatopharmacology and Ethnopharmacology, School of Pharmaceutical Sciences, South-Central Minzu University, No. 182, Minyuan Road, Wuhan 430074, China.
Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, No. 818 Fenghua Road, Jiangbei District, Ningbo 315211, China.
Int J Mol Sci. 2023 Sep 15;24(18):14162. doi: 10.3390/ijms241814162.
Overconsumption of high-fat foods increases the risk of fatty liver disease (FLD) and liver cancer with long pathogenic cycles. It is also known that the intake of the chemical poison nitrosamine and its nanopreparations can promote the development of liver injuries, such as FLD, and hepatic fibrosis, and significantly shorten the formation time of the liver cancer cycle. The present work confirmed that the coexposure of a high-fat diet (HFD) and nano-diethylnitrosamine (nano-DEN) altered the tumor microenvironment and studied the effect of this coexposure on the progression of fatty liver malignant transformation into liver cancer. Gene transcriptomics and immunostaining were used to evaluate the tumor promotion effect of the coexposure in mice. After coexposure treatment, tumor nodules were obviously increased, and inflammation levels were elevated. The liver transcriptomics analysis showed that the expression levels of inflammatory, fatty, and fibrosis-related factors in the coexposed group were increased in comparison with the nano-DEN- and high-fat-alone groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that coexposure aggravated the high expression of genes related to the carcinomatous pathway and accelerated the formation of the tumor microenvironment. The immunohistochemical staining results showed that the coexposure significantly increased the abnormal changes in proteins related to inflammation, proliferation, aging, and hypoxia in mouse liver tissues. The coexposure of high fat and nano-DEN aggravated the process of steatosis and carcinogenesis. In conclusion, the habitual consumption of pickled foods containing nitrosamines in a daily HFD significantly increases the risk of liver pathology lesions progressing from FLD to liver cancer.
过量食用高脂肪食物会增加患脂肪肝疾病（FLD）和肝癌的风险，且致病周期较长。众所周知，化学毒物亚硝胺及其纳米制剂的摄入会促进肝脏损伤（如FLD）和肝纤维化的发展，并显著缩短肝癌周期的形成时间。本研究证实，高脂饮食（HFD）与纳米二乙基亚硝胺（nano-DEN）共同暴露会改变肿瘤微环境，并研究这种共同暴露对脂肪肝恶性转化为肝癌进程的影响。采用基因转录组学和免疫染色法评估共同暴露对小鼠的促肿瘤作用。共同暴露处理后，肿瘤结节明显增多，炎症水平升高。肝脏转录组学分析表明，与单独使用纳米DEN和高脂组相比，共同暴露组中炎症、脂肪和纤维化相关因子的表达水平升高。京都基因与基因组百科全书（KEGG）结果显示，共同暴露加剧了与癌途径相关基因的高表达，加速了肿瘤微环境的形成。免疫组化染色结果表明，共同暴露显著增加了小鼠肝组织中与炎症、增殖、衰老和缺氧相关蛋白质的异常变化。高脂肪与纳米DEN共同暴露加剧了脂肪变性和致癌过程。总之，在日常高脂饮食中习惯性食用含有亚硝胺的腌制食品会显著增加肝脏病理损伤从FLD发展为肝癌的风险。
