title: Fish oil alleviated high-fat diet-induced non-alcoholic fatty liver disease via regulating hepatic lipids metabolism and metaflammation: a transcriptomic study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Wuhan Polytechnic University, School of Biology and Pharmaceutical Engineering, Wuhan, Hubei, 430023, China. yuanfh@jhun.edu.cn.|Jianghan University, School of Medicine, Wuhan, China. yuanfh@jhun.edu.cn.
authors.forename: Fahu
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Wuhan Polytechnic University, School of Biology and Pharmaceutical Engineering, Wuhan, Hubei, 430023, China. wanghualin313@gmail.com.
authors.forename: Hualin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Wuhan Polytechnic University, School of Biology and Pharmaceutical Engineering, Wuhan, Hubei, 430023, China. tianyupost@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Wuhan Polytechnic University, School of Biology and Pharmaceutical Engineering, Wuhan, Hubei, 430023, China. liqi3956613@qq.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Blood Transfusion, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. atoprine@qq.com.
authors.forename: Lei
authors.initials: L
authors.lastname: He
authors.affiliation: Wuhan Polytechnic University, School of Biology and Pharmaceutical Engineering, Wuhan, Hubei, 430023, China. lina81518@qq.com.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Wuhan Polytechnic University, School of Biology and Pharmaceutical Engineering, Wuhan, Hubei, 430023, China. zhiguo_l@126.com.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D059305:Diet, High-Fat; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D005247:Feeding Behavior; D005395:Fish Oils / Q000494:pharmacology / Q000627:therapeutic use*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis; D006949:Hyperlipidemias / Q000188:drug therapy; D007249:Inflammation / Q000150:complications / Q000188:drug therapy; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA; D000637:Transaminases / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics*
chemical_list: D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D012333:RNA, Messenger; D002784:Cholesterol; D000637:Transaminases
references.citation: Dig Dis Sci. 2011 Oct;56(10):3045-52
references.pmid: 21516322
references.citation: Eur J Intern Med. 2004 Feb;15(1):10-21
references.pmid: 15066643
references.citation: Nutr Metab (Lond). 2007 Feb 21;4:4
references.pmid: 17313679
references.citation: J Nutr Biochem. 2008 Sep;19(9):567-76
references.pmid: 18430557
references.citation: PLoS One. 2013;8(6):e65247
references.pmid: 23762326
references.citation: Biochim Biophys Acta. 2000 Jun 26;1486(1):1-17
references.pmid: 10856709
references.citation: Prog Lipid Res. 2013 Jan;52(1):175-91
references.pmid: 23206728
references.citation: Bioinformatics. 2010 Jan 1;26(1):139-40
references.pmid: 19910308
references.citation: J Clin Invest. 2005 May;115(5):1343-51
references.pmid: 15864352
references.citation: World J Gastroenterol. 2014 Jul 21;20(27):9038-49
references.pmid: 25083077
references.citation: J Lipid Res. 2006 Jan;47(1):181-92
references.pmid: 16222032
references.citation: Hepatology. 2011 Sep 2;54(3):837-45
references.pmid: 21674556
references.citation: Bioinformatics. 2009 May 1;25(9):1105-11
references.pmid: 19289445
references.citation: J Hepatol. 2012 Apr;56(4):944-51
references.pmid: 22023985
references.citation: Biomed Res Int. 2014;2014:310981
references.pmid: 24967351
references.citation: Hepatology. 2005 Jun;41(6):1313-21
references.pmid: 15915461
references.citation: Dig Liver Dis. 2015 Dec;47(12):997-1006
references.pmid: 26454786
references.citation: Am J Clin Nutr. 2009 Feb;89(2):558-67
references.pmid: 19141695
references.citation: J Hepatol. 2013 Oct;59(4):859-71
references.pmid: 23751754
references.citation: Hepatology. 2003 Apr;37(4):909-16
references.pmid: 12668986
references.citation: Annu Rev Immunol. 2011;29:415-45
references.pmid: 21219177
references.citation: Lipids. 2005 Jan;40(1):31-8
references.pmid: 15825828
references.citation: PLoS One. 2010;5(10):e13577
references.pmid: 21042596
references.citation: Hepatology. 2010 Nov;52(5):1836-46
references.pmid: 21038418
references.citation: Vascul Pharmacol. 2016 Jan;76:37-41
references.pmid: 26143741
references.citation: J Gastroenterol. 2013 Apr;48(4):434-41
references.pmid: 23397118
references.citation: Dig Liver Dis. 2015 Mar;47(3):181-90
references.pmid: 25739820
references.citation: Genome Biol. 2009;10(3):R25
references.pmid: 19261174
references.citation: J Clin Gastroenterol. 2006 Mar;40 Suppl 1:S17-29
references.pmid: 16540762
references.citation: Trends Endocrinol Metab. 2008 Mar;19(2):65-73
references.pmid: 18291668
references.citation: Clin Nutr. 2011 Feb;30(1):6-19
references.pmid: 20619513
references.citation: Hepatol Res. 2007 Jan;37(1):50-7
references.pmid: 17300698
references.citation: Nat Genet. 2005 Feb;37(2):161-5
references.pmid: 15654334
references.citation: Proc Natl Acad Sci U S A. 2001 May 22;98(11):6027-32
references.pmid: 11371634
references.citation: Gastroenterology. 1998 Apr;114(4):842-5
references.pmid: 9547102
references.citation: Arch Med Res. 2011 Jul;42(5):337-53
references.pmid: 21843565
references.citation: Hepatology. 2004 Mar;39(3):608-16
references.pmid: 14999679
references.citation: J Biol Chem. 1999 Aug 13;274(33):23577-83
references.pmid: 10438539
references.citation: J Biol Chem. 2009 Nov 13;284(46):31726-34
references.pmid: 19759400
references.citation: J Lipid Res. 2009 Apr;50 Suppl:S80-5
references.pmid: 18997165
references.citation: J Nutr. 1993 Nov;123(11):1939-51
references.pmid: 8229312
references.citation: Curr Opin Lipidol. 2014 Oct;25(5):387-93
references.pmid: 25110901
references.citation: Nature. 2010 Jul 29;466(7306):627-31
references.pmid: 20562852
references.citation: FASEB J. 2012 Aug;26(8):3282-91
references.pmid: 22562833
references.citation: Metabolism. 2016 Aug;65(8):1136-50
references.pmid: 26477269
references.citation: Am J Physiol Gastrointest Liver Physiol. 2008 Apr;294(4):G839-43
references.pmid: 18276831