PMID- 33045621
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20210618
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 37
DP  - 2020 Oct
TI  - Homocysteine promotes hepatic steatosis by activating the adipocyte lipolysis in 
      a HIF1alpha-ERO1alpha-dependent oxidative stress manner.
PG  - 101742
LID - S2213-2317(20)30947-2 [pii]
LID - 10.1016/j.redox.2020.101742 [doi]
LID - 101742
AB  - Hyperhomocysteinemia (HHcy) is related to liver diseases, such as nonalcoholic 
      fatty liver (NAFL). Although the precise pathogenesis of NAFL is still largely 
      unknown, the links between organs seem to play a vital role. The current study 
      aimed to explore the role of white adipose tissue in homocysteine (Hcy)-induced 
      NAFL. Blood samples from nonhyperhomocysteinemia or hyperhomocysteinemia 
      individuals were collected to assess correlation between Hcy and triglyceride 
      (TG) or free fatty acids (FFAs) levels. C57BL/6 mice were maintained on a 
      high-methionine diet or administered with Hcy (1.8 g/L) in the drinking water to 
      establish an HHcy mouse model. We demonstrated that Hcy activated adipocyte 
      lipolysis and that this change was accompanied by an increased release of FFAs 
      and glycerol. Excessive FFAs were taken up by hepatocyte, which resulted in lipid 
      accumulation in the liver. Treatment with acipimox (0.08 g kg (-1) day (-1)), a 
      potent chemical inhibitor of lipolysis, markedly decreased Hcy-induced NAFL. 
      Mechanistically, hypoxia-inducible factor 1alpha (HIF1alpha)-endoplasmic reticulum 
      oxidoreductin 1alpha (ERO1alpha) mediated pathway promoted H(2)O(2) accumulation and 
      induced endoplasmic reticulum (ER) overoxidation, ER stress and more closed 
      ER-lipid droplet interactions, which were responsible for activating the 
      lipolytic response. In conclusion, this study reveals that Hcy activates 
      adipocyte lipolysis and suggests the potential utility of targeted ER redox 
      homeostasis for treating Hcy-induced NAFL.
CI  - Copyright (c) 2020 The Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Yan, Yu
AU  - Yan Y
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry 
      of Education, Beijing, 100191, PR China.
FAU - Wu, Xun
AU  - Wu X
AD  - National Laboratory of Biomacromolecules, CAS Center for Excellence in 
      Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 
      100101, PR China; College of Life Sciences, University of Chinese Academy of 
      Sciences, Beijing, 100049, PR China.
FAU - Wang, Pengcheng
AU  - Wang P
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry 
      of Education, Beijing, 100191, PR China.
FAU - Zhang, Songyang
AU  - Zhang S
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry 
      of Education, Beijing, 100191, PR China.
FAU - Sun, Lulu
AU  - Sun L
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry 
      of Education, Beijing, 100191, PR China.
FAU - Zhao, Yang
AU  - Zhao Y
AD  - Department of Laboratory Medicine, Peking University Third Hospital, Beijing, 
      100191, PR China.
FAU - Zeng, GuangYi
AU  - Zeng G
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry 
      of Education, Beijing, 100191, PR China.
FAU - Liu, Bo
AU  - Liu B
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry 
      of Education, Beijing, 100191, PR China.
FAU - Xu, Guoheng
AU  - Xu G
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry 
      of Education, Beijing, 100191, PR China.
FAU - Liu, Huiying
AU  - Liu H
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry 
      of Education, Beijing, 100191, PR China.
FAU - Wang, Lei
AU  - Wang L
AD  - National Laboratory of Biomacromolecules, CAS Center for Excellence in 
      Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 
      100101, PR China; College of Life Sciences, University of Chinese Academy of 
      Sciences, Beijing, 100049, PR China. Electronic address: wanglei@ibp.ac.cn.
FAU - Wang, Xian
AU  - Wang X
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry 
      of Education, Beijing, 100191, PR China. Electronic address: xwang@bjmu.edu.cn.
FAU - Jiang, Changtao
AU  - Jiang C
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry 
      of Education, Beijing, 100191, PR China; Center of Basic Medical Research, 
      Institute of Medical Innovation and Research, Third Hospital, Peking University, 
      Beijing, 100191, PR China; Center for Obesity and Metabolic Disease Research, 
      School of Basic Medical Sciences, Peking University, Beijing, 100191, PR China. 
      Electronic address: jiangchangtao@bjmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201001
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - BBX060AN9V (Hydrogen Peroxide)
SB  - IM
MH  - Adipocytes
MH  - Animals
MH  - Endoplasmic Reticulum Stress
MH  - *Homocysteine
MH  - Hydrogen Peroxide
MH  - *Lipolysis
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxidative Stress
PMC - PMC7559542
OTO - NOTNLM
OT  - Adipocyte lipolysis
OT  - ER oxidoreductin 1alpha
OT  - Hyperhomocysteinemia
OT  - Hypoxia-inducible factor 1alpha
OT  - Nonalcoholic fatty liver
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper. The authors declare the following financial interests/personal 
      relationships which may be considered as potential competing interests:
EDAT- 2020/10/13 06:00
MHDA- 2021/06/22 06:00
PMCR- 2020/10/01
CRDT- 2020/10/12 20:13
PHST- 2020/01/20 00:00 [received]
PHST- 2020/09/25 00:00 [revised]
PHST- 2020/09/28 00:00 [accepted]
PHST- 2020/10/13 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/10/12 20:13 [entrez]
PHST- 2020/10/01 00:00 [pmc-release]
AID - S2213-2317(20)30947-2 [pii]
AID - 101742 [pii]
AID - 10.1016/j.redox.2020.101742 [doi]
PST - ppublish
SO  - Redox Biol. 2020 Oct;37:101742. doi: 10.1016/j.redox.2020.101742. Epub 2020 Oct 
      1.