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Background  Intake 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.    Methods  Ten 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).    Results  The 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 genes  per2  and  per3 , 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 as  Srebf1 ,  Fasn ,  Scd1 ,  Insig2 ,  Cd36 ,  Cyp7a1 ,  Abcg5 ,  Abcg8  and  Pcsk9 . Moreover, the expression levels of pro-inflammation genes  Mcp1 ,  Socs2 ,  Sema4a , and  Cd44  in the FOH group were lower than that of WD group, implying that fish oil protects the liver against WD-induced hepatic inflammation.    Conclusion  The 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.    Electronic supplementary material  The online version of this article (doi:10.1186/s12944-016-0190-y) contains supplementary material, which is available to authorized users.

lipids in health and disease

Fish oil alleviated high-fat diet–induced non-alcoholic fatty liver disease via regulating hepatic lipids metabolism and metaflammation: a transcriptomic study