n-3 PUFAs reduce tumor load and improve survival in a NASH-tumor mouse model
n-3 PUFAs reduce tumor load and improve survival in a NASH-tumor mouse model
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DOI：
10.1177/2040622319872118
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发表时间：
2019-09-01
影响因子：
3.5
通讯作者：
Abshagen, Kerstin
中科院分区：
文献类型：
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作者：
Liebig, Marie;Dannenberger, Dirk;Abshagen, Kerstin
背景：肝细胞癌占所有癌症死亡的9.1%，是全球癌症死亡的第二大原因。由于代谢综合征的患病率不断增加，非酒精性脂肪肝（NAFLD）已演变为肝细胞癌发展的主要危险因素。在此，我们研究了膳食n-3多不饱和脂肪酸（PUFA）补充剂是否能改善进行性NAFLD的结局。研究方法：喂养三种高脂饮食，n-3和n-6 PUFA含量和比例不同（n-3/n-6：1：8，1：1，5：1），在12周龄和20周龄链脲佐菌素/高脂饮食（STZ/HFD）治疗的小鼠中分析n-3 PUFA和n-3/n-6 PUFA比例对NAFLD相关肝纤维化和肿瘤发生的影响。结果如下：饲喂富含n-3 PUFA的饲料（1：1和5：1）可导致肝脏n-3 PUFA含量和n-3/n-6 PUFA比值增加，肝脏脂质蓄积减少。在20周龄的小鼠中，富含n-3 PUFA的饮食显著减轻了肿瘤负荷，降低了肝脏/体重指数、肿瘤大小和肿瘤数量。最后，这些效果伴随着这些小鼠存活率的显著改善。结论：在此，我们表明，增加n-3 PUFA含量和n-3/n-6 PUFA比率导致STZ/HFD治疗小鼠的存活率提高和肿瘤进展减弱。因此，n-3 PUFA可能是针对NAFLD相关肿瘤发生的新治疗选择的基础。
Background: With 9.1% of all cancer deaths, hepatocellular carcinoma is the second leading cause of cancer deaths worldwide. Due to the increasing prevalence of metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) has evolved into a major risk factor for hepatocellular carcinoma development. Herein, we investigated whether a dietary n-3 polyunsaturated fatty acid (PUFA) supplementation improves the outcome of progressive NAFLD. Methods: Feeding three high-fat diets, differing in n-3 and n-6 PUFA contents and ratios (n-3/n-6: 1:8, 1:1, 5:1), the impact of n-3 PUFAs and n-3/n-6 PUFA ratios on NAFLD-related liver fibrosis and tumorigenesis was analyzed in 12- and 20-week-old streptozotocin/high-fat diet (STZ/HFD)-treated mice. Results: Feeding of n-3 PUFA-rich diets (1:1 and 5:1) resulted in increased hepatic n-3 PUFA content and n-3/n-6 PUFA ratio with decreased hepatic lipid accumulation. In 20-week-old mice, n-3 PUFA-rich diets alleviated tumor load significantly, with reduced liver/body weight index, tumor size, and tumor number. Finally, these effects were accompanied by a significant improvement of survival of these mice. Conclusions: Herein, we showed that increased n-3 PUFA content and n-3/n-6 PUFA ratios lead to improved survival and attenuated tumor progression in STZ/HFD-treated mice. Thus, n-3 PUFAs could be the basis for new therapeutic options against NAFLD-related tumorigenesis.