title: Differential regulation of protein expression in response to polyunsaturated fatty acids in the liver of apoE-knockout mice and in HepG2 cells.
abstract: BACKGROUND
  Polyunsaturated fatty acids (PUFAs) are nutrients necessary for life. The liver is the essential metabolic center, which aids in maintaining health via diverse biological actions. In the present work, a proteomics study was conducted with an aim to provide new insights into PUFA-regulated hepatic protein expression in apoE-knockout mice. Additionally, we investigated how n-3 PUFAs influence cytokine-challenge by using HepG2 cells as a model.
  
  
  RESULTS
  Through the proteomic analysis using 2-dimensional electrophoresis and mass spectrometry, we found that 28, 23, 14, and 28 hepatic proteins were up-regulated at least a two-fold difference in intensity compared with the control group in mice treated with the docosahexaenoic acid, eicosapentaenoic acid, arachidonic acid, and linoleic acid, respectively. In contrast, 12 hepatic proteins were down-regulated with a ratio value of less than 0.5 compared to their control counterparts by these four fatty acids. All of the altered proteins were then sorted according to their biochemical properties related to metabolism, redox stress/inflammation, enzymatic reactions, and miscellaneous functions. The results provide evidence that PUFAs may act as either pro-inflammatory or anti-inflammatory agents. Cytokine-challenged HepG2 cells were used to reveal the anti-inflammatory function of n-3 PUFAs. The results showed that interleukin (IL)-1β combined with IL-6 induced C-reactive protein (CRP) mRNA expression and its protein secretion by HepG2 cells. The CRP promoter activity was significantly increased in the IL-6-treated cells, whereas IL-1β alone had no effect. However, IL-1β and IL-6 acted synergistically to further enhance CRP promoter activities. Furthermore, n-3 PUFAs inhibited nuclear factor-κB (NF-κB) activation and the phosphorylation of the nuclear signal transducer and activator of transcription 3 (STAT3) during cytokine-induced CRP production.
  
  
  CONCLUSIONS
  This study indicates that PUFAs induced changes in the hepatic protein profile in vivo. Furthermore, n-3 PUFAs exert their anti-inflammatory properties through differential molecular mechanisms in hepatic cells. These results provide novel information regarding the roles of PUFAs in the liver at the tissue and cellular levels.
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No.155, Sec.2, Li-Nong Street, Taipei, 11221, Taiwan. Huang.edcc@gmail.com.
authors.forename: Chun-Ying
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, 61363, Taiwan. b8902030@gmail.com.|Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan. b8902030@gmail.com.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Chen
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No.155, Sec.2, Li-Nong Street, Taipei, 11221, Taiwan. ygtsay@ym.edu.tw.
authors.forename: Yeou-Guang
authors.initials: YG
authors.lastname: Tsay
authors.affiliation: Institute of Food Science and Technology, National Taiwan University, Taipei, 10617, Taiwan. scjhsieh@ntu.edu.tw.
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Hsieh
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No.155, Sec.2, Li-Nong Street, Taipei, 11221, Taiwan. u9223015@gmail.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Medical Research, Taichung Veterans General Hospital, Taichung, 40354, Taiwan. wjlee@vghtc.gov.tw.
authors.forename: Wen-Jane
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Medical Research, Taichung Veterans General Hospital, Taichung, 40354, Taiwan. whhsheu@vghtc.gov.tw.
authors.forename: Wayne Huey-Herng
authors.initials: WH
authors.lastname: Sheu
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No.155, Sec.2, Li-Nong Street, Taipei, 11221, Taiwan. anchia@ym.edu.tw.
authors.forename: An-Na
authors.initials: AN
authors.lastname: Chiang
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D005231:Fatty Acids, Unsaturated; D012333:RNA, Messenger; D002097:C-Reactive Protein