PMID- 31300810
OWN - NLM
STAT- MEDLINE
DCOM- 20200831
LR  - 20210923
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 41
IP  - 2
DP  - 2020 Apr 22
TI  - A trans-fatty acid-rich diet promotes liver tumorigenesis in HCV core gene 
      transgenic mice.
PG  - 159-170
LID - 10.1093/carcin/bgz132 [doi]
AB  - Excess consumption of trans-fatty acid (TFA), an unsaturated fatty acid 
      containing trans double bonds, is a major risk factor for cardiovascular disease 
      and metabolic syndrome. However, little is known about the link between TFA and 
      hepatocellular carcinoma (HCC) despite it being a frequent form of cancer in 
      humans. In this study, the impact of excessive dietary TFA on hepatic 
      tumorigenesis was assessed using hepatitis C virus (HCV) core gene transgenic 
      mice that spontaneously developed HCC. Male transgenic mice were treated for 5 
      months with either a control diet or an isocaloric TFA-rich diet that replaced 
      the majority of soybean oil with shortening. The prevalence of liver tumors was 
      significantly higher in TFA-rich diet-fed transgenic mice compared with control 
      diet-fed transgenic mice. The TFA-rich diet significantly increased the 
      expression of pro-inflammatory cytokines, as well as oxidative and endoplasmic 
      reticulum stress, and activated nuclear factor-kappa B (NF-kappaB) and nuclear factor 
      erythroid 2-related factor 2 (NRF2), leading to high p62/sequestosome 1 (SQSTM1) 
      expression. Furthermore, the TFA diet activated extracellular signal-regulated 
      kinase (ERK) and stimulated the Wnt/beta-catenin signaling pathway, synergistically 
      upregulating cyclin D1 and c-Myc, driving cell proliferation. Excess TFA intake 
      also promoted fibrogenesis and ductular reaction, presumably contributing to 
      accelerated liver tumorigenesis. In conclusion, these results demonstrate that a 
      TFA-rich diet promotes hepatic tumorigenesis, mainly due to persistent activation 
      of NF-kappaB and NRF2-p62/SQSTM1 signaling, ERK and Wnt/beta-catenin pathways and 
      fibrogenesis. Therefore, HCV-infected patients should avoid a TFA-rich diet to 
      prevent liver tumor development.
CI  - (c) The Author(s) 2019. Published by Oxford University Press. All rights reserved. 
      For Permissions, please email: journals.permissions@oup.com.
FAU - Hu, Xiao
AU  - Hu X
AD  - Department of Metabolic Regulation, Shinshu University School of Medicine, 
      Matsumoto, Japan.
AD  - Department of Pathophysiology, Hebei Medical University, Shijiazhuang, People's 
      Republic of China.
FAU - Wang, Xiaojing
AU  - Wang X
AD  - Department of Metabolic Regulation, Shinshu University School of Medicine, 
      Matsumoto, Japan.
AD  - Department of Gastroenterology, Lishui Hospital, Zhejiang University School of 
      Medicine, Lishui, Zhejiang, People's Republic of China.
FAU - Jia, Fangping
AU  - Jia F
AD  - Department of Metabolic Regulation, Shinshu University School of Medicine, 
      Matsumoto, Japan.
FAU - Tanaka, Naoki
AU  - Tanaka N
AD  - Department of Metabolic Regulation, Shinshu University School of Medicine, 
      Matsumoto, Japan.
AD  - Research Center for Social Systems, Shinshu University, Matsumoto, Japan.
FAU - Kimura, Takefumi
AU  - Kimura T
AD  - Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto, 
      Japan.
FAU - Nakajima, Takero
AU  - Nakajima T
AD  - Department of Metabolic Regulation, Shinshu University School of Medicine, 
      Matsumoto, Japan.
FAU - Sato, Yoshiko
AU  - Sato Y
AD  - Department of Molecular Pathology, Shinshu University School of Medicine, 
      Matsumoto, Japan.
FAU - Moriya, Kyoji
AU  - Moriya K
AD  - Department of Infection Control and Prevention, The University of Tokyo, Tokyo, 
      Japan.
FAU - Koike, Kazuhiko
AU  - Koike K
AD  - Department of Gastroenterology, The University of Tokyo, Tokyo, Japan.
FAU - Gonzalez, Frank J
AU  - Gonzalez FJ
AD  - Laboratory of Metabolism, National Cancer Institute, National Institutes of 
      Health, Bethesda, MD, USA.
FAU - Nakayama, Jun
AU  - Nakayama J
AD  - Department of Molecular Pathology, Shinshu University School of Medicine, 
      Matsumoto, Japan.
FAU - Aoyama, Toshifumi
AU  - Aoyama T
AD  - Department of Metabolic Regulation, Shinshu University School of Medicine, 
      Matsumoto, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Dietary Fats)
RN  - 0 (Trans Fatty Acids)
RN  - 0 (Viral Core Proteins)
RN  - 0 (nucleocapsid protein, Hepatitis C virus)
SB  - IM
MH  - Animals
MH  - Carcinogenesis/pathology
MH  - Carcinoma, Hepatocellular/genetics/*pathology/prevention & control/virology
MH  - Cell Proliferation
MH  - Dietary Fats/administration & dosage/*adverse effects
MH  - Disease Models, Animal
MH  - Fibrosis
MH  - Hepacivirus/genetics/pathogenicity
MH  - Hepatitis C/genetics/*pathology/virology
MH  - Humans
MH  - Liver/pathology
MH  - Liver Neoplasms/genetics/*pathology/prevention & control/virology
MH  - MAP Kinase Signaling System
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Risk Factors
MH  - Trans Fatty Acids/administration & dosage/*adverse effects
MH  - Up-Regulation
MH  - Viral Core Proteins/genetics
MH  - Wnt Signaling Pathway
PMC - PMC8456504
EDAT- 2019/07/14 06:00
MHDA- 2020/09/01 06:00
PMCR- 2020/07/12
CRDT- 2019/07/14 06:00
PHST- 2018/12/23 00:00 [received]
PHST- 2019/06/08 00:00 [revised]
PHST- 2019/07/11 00:00 [accepted]
PHST- 2019/07/14 06:00 [pubmed]
PHST- 2020/09/01 06:00 [medline]
PHST- 2019/07/14 06:00 [entrez]
PHST- 2020/07/12 00:00 [pmc-release]
AID - 5531913 [pii]
AID - bgz132 [pii]
AID - 10.1093/carcin/bgz132 [doi]
PST - ppublish
SO  - Carcinogenesis. 2020 Apr 22;41(2):159-170. doi: 10.1093/carcin/bgz132.