PMID- 30973961
OWN - NLM
STAT- MEDLINE
DCOM- 20200605
LR  - 20200605
IS  - 1873-3468 (Electronic)
IS  - 0014-5793 (Linking)
VI  - 593
IP  - 10
DP  - 2019 May
TI  - Orphan nuclear receptor NR4A1 suppresses hyperhomocysteinemia-induced hepatic 
      steatosis in vitro and in vivo.
PG  - 1061-1071
LID - 10.1002/1873-3468.13384 [doi]
AB  - Homocysteine (Hcy) is associated with nonalcoholic fatty liver disease (NAFLD). 
      orphan nuclear receptor subfamily 4 group A member 1 (NR4A1) is involved in 
      hepatic lipid metabolism. However, the potential role of NR4A1 in Hcy-associated 
      NAFLD remains elusive. We aimed to elucidate the regulation of NR4A1 and its 
      significance in Hcy-induced NAFLD. Hcy induced steatosis and elevated the 
      expression of CD36 and FATP2 in HepG2 cells. Furthermore, Hcy enhanced p300 and 
      decreased HDAC7 recruitment to the NR4A1 promoter, resulting in histone H3K27 
      hyperacetylation and NR4A1 upregulation. Moreover, NR4A1 depletion not only 
      mimicked but also exaggerated the effects of Hcy on steatosis, whereas NR4A1 
      agonist Cytosporone B (CsnB) blocked Hcy-induced steatosis. In 
      hyperhomocysteinemia (HHcy) mice, CsnB attenuated HHcy-induced hepatic steatosis. 
      Thus, Hcy transiently and rapidly induces NR4A1 expression to reduce Hcy-induced 
      steatosis.
CI  - (c) 2019 Federation of European Biochemical Societies.
FAU - Liang, Hongjin
AU  - Liang H
AUID- ORCID: 0000-0003-2630-6756
AD  - Department of Cell Biology and Genetics, Key Laboratory of Molecular Biology in 
      High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education 
      Institutes, Shantou University Medical College, China.
AD  - Department of Rheumatology, the First Affiliated Hospital, Shantou University 
      Medical College, China.
FAU - Xie, Xina
AU  - Xie X
AD  - Department of Cell Biology and Genetics, Key Laboratory of Molecular Biology in 
      High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education 
      Institutes, Shantou University Medical College, China.
AD  - Health Science Center, Institute of Translational Medicine, Shenzhen Second 
      People's Hospital, the First Affiliated Hospital of Shenzhen University, China.
FAU - Song, Xuhong
AU  - Song X
AD  - Department of Cell Biology and Genetics, Key Laboratory of Molecular Biology in 
      High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education 
      Institutes, Shantou University Medical College, China.
FAU - Huang, Meihui
AU  - Huang M
AD  - Department of Cell Biology and Genetics, Key Laboratory of Molecular Biology in 
      High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education 
      Institutes, Shantou University Medical College, China.
AD  - Department of Pathology and Central Laboratory, Shantou Central Hospital, 
      Affiliated Shantou Hospital of Sun Yat-sen University, China.
FAU - Su, Ting
AU  - Su T
AD  - Department of Cell Biology and Genetics, Key Laboratory of Molecular Biology in 
      High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education 
      Institutes, Shantou University Medical College, China.
FAU - Chang, Xiaolan
AU  - Chang X
AD  - Department of Cell Biology and Genetics, Key Laboratory of Molecular Biology in 
      High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education 
      Institutes, Shantou University Medical College, China.
FAU - Liang, Bin
AU  - Liang B
AD  - Department of Cell Biology and Genetics, Key Laboratory of Molecular Biology in 
      High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education 
      Institutes, Shantou University Medical College, China.
FAU - Huang, Dongyang
AU  - Huang D
AD  - Department of Cell Biology and Genetics, Key Laboratory of Molecular Biology in 
      High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education 
      Institutes, Shantou University Medical College, China.
LA  - eng
GR  - 31770876/National Natural Science Foundation of China/International
GR  - 81400616/National Natural Science Foundation of China/International
GR  - 81470441/National Natural Science Foundation of China/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190422
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (Nuclear Receptor Subfamily 4, Group A, Member 1)
SB  - IM
MH  - Animals
MH  - Fatty Liver/etiology/genetics/*metabolism/prevention & control
MH  - Gene Expression Regulation
MH  - Hep G2 Cells
MH  - Humans
MH  - Hyperhomocysteinemia/*complications
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nuclear Receptor Subfamily 4, Group A, Member 1/genetics/*metabolism
OTO - NOTNLM
OT  - NR4A1
OT  - histone H3K27 acetylation
OT  - homocysteine
OT  - nonalcoholic fatty liver disease
OT  - steatosis
EDAT- 2019/04/12 06:00
MHDA- 2020/06/06 06:00
CRDT- 2019/04/12 06:00
PHST- 2018/12/20 00:00 [received]
PHST- 2019/03/20 00:00 [revised]
PHST- 2019/04/08 00:00 [accepted]
PHST- 2019/04/12 06:00 [pubmed]
PHST- 2020/06/06 06:00 [medline]
PHST- 2019/04/12 06:00 [entrez]
AID - 10.1002/1873-3468.13384 [doi]
PST - ppublish
SO  - FEBS Lett. 2019 May;593(10):1061-1071. doi: 10.1002/1873-3468.13384. Epub 2019 
      Apr 22.