Fish oil alleviated high-fat diet-induced non-alcoholic fatty liver disease via regulating hepatic lipids metabolism and metaflammation: a transcriptomic study.
Fish oil alleviated high-fat diet-induced non-alcoholic fatty liver disease via regulating hepatic lipids metabolism and metaflammation: a transcriptomic study.
复制标题
鱼油通过调节肝脂代谢和代谢炎症缓解高脂饮食诱发的非酒精性脂肪肝：转录组研究
DOI：
10.1186/s12944-016-0190-y
复制
发表时间：
2016-02-01
影响因子：
4.5
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Yuan F;Wang H;Tian Y;Li Q;He L;Li N;Liu Z
背景摄入富含n-3多不饱和脂肪酸(PUFAs)的鱼油被认为有助于预防非酒精性脂肪性肝病(NAFLD)的发生。然而，潜在的机制仍不清楚。本研究旨在进一步了解鱼油对非酒精性脂肪肝的保护作用机制。方法雄性SD大鼠10只，分别喂以对照饲料(CON)、西式高脂高胆固醇饲料(WD)和含鱼油的WD饲料(FOH)，共16周。组织学和生化检查证实肝脂肪变性和肝纤维化的发生。结果食用鱼油可明显改善WD所致的高脂血症、转氨酶升高、肝脏脂肪变性、炎性细胞浸润和肝纤维化。肝脏RNA-Seq分析表明，长期摄入鱼油恢复了生物钟相关基因per2和per3的表达，而在WD喂养的动物中，这两个基因的表达减少。食用鱼油还纠正了与脂肪酸和胆固醇代谢有关的基因的表达水平，如Srebf1、FASN、Scd1、Insig2、CD36、Cyp7a1、Abcg5、Abcg8和Pcsk9。此外，FOH组促炎症基因Mcp1、Socs2、Sema4a和CD44的表达水平低于WD组，提示鱼油对WD诱导的肝脏炎症具有保护作用。结论鱼油通过改善脂代谢，减轻肝脏炎症，对WD诱导的NALFD具有保护作用。我们的发现增加了目前对n-3多不饱和脂肪酸对抗非酒精性脂肪肝益处的理解。
BackgroundIntake of fish oil rich in n-3 polyunsaturated fatty acids (PUFAs) is believed to be beneficial against development of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms remain unclear. This study was to gain further understanding of the potential mechanisms of the protective effects of fish oil against NAFLD.MethodsTen male Sprague–Dawley rats were fed a control diet (CON), a Western style high-fat and high-cholesterol diet (WD), or a WD diet containing fish oil (FOH) for 16 weeks respectively. The development of liver steatosis and fibrosis were verified by histological and biochemical examination. Hepatic transcriptome were extracted for RNA-seq analysis, and particular results were confirmed by real-time polymerase chain reaction (PCR).ResultsThe consumption of fish oil significantly ameliorated WD-induced dyslipidemia, transaminase elevation, hepatic steatosis, inflammatory infiltration, and fibrosis. Hepatic RNA-Seq analysis showed that long-term intake of fish oil restored the expression of circadian clock-related genesper2andper3, which were reduced in WD fed animals. Fish oil consumption also corrected the expression levels of genes involved in fatty acid and cholesterol metabolism, such asSrebf1,Fasn,Scd1,Insig2,Cd36,Cyp7a1,Abcg5,Abcg8andPcsk9. Moreover, the expression levels of pro-inflammation genesMcp1,Socs2,Sema4a, andCd44in the FOH group were lower than that of WD group, implying that fish oil protects the liver against WD-induced hepatic inflammation.ConclusionThe present study demonstrates fish oil protects against WD-induced NALFD via improving lipid metabolism and ameliorating hepatic inflammation. Our findings add to the current understanding on the benefits of n-3 PUFAs against NAFLD.