PMID- 28933423
OWN - NLM
STAT- MEDLINE
DCOM- 20180723
LR  - 20181201
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 38
IP  - 12
DP  - 2017 Dec
TI  - Omega-3 PUFA ameliorates hyperhomocysteinemia-induced hepatic steatosis in mice 
      by inhibiting hepatic ceramide synthesis.
PG  - 1601-1610
LID - 10.1038/aps.2017.127 [doi]
AB  - Hyperhomocysteinemia (HHcy) is a key risk factor in hepatic steatosis. In this 
      study, we applied a metabolomic approach to investigate the changes in the 
      metabolite profile due to HHcy-induced hepatic steatosis and the effects of 
      omega-3 PUFA (polyunsaturated fatty acid) supplementation in mice. HHcy was 
      induced in mice by giving DL-Hcy (1.8 g/L) in drinking water for 6 weeks, then 
      the mice were sacrificed, and the metabolic profiles of the liver and plasma were 
      analyzed through UPLC-ESI-QTOFMS-based lipidomics. Hepatic triglycerides and 
      cholesterol were further assayed. The expression of ceramide metabolism-related 
      genes was measured by quantitative PCR. Compared with control mice, HHcy mice 
      exhibited hepatic steatosis with a notable increase in ceramide-related 
      metabolites and subsequent upregulation of ceramide synthesis genes such as 
      Sptlc3, Degs2, Cer4 and Smpd4. Omega-3 PUFA was simultaneously administered in 
      HHcy mice through chow diet containing 3.3% omega-3 PUFA supplement for 6 weeks, 
      which significantly ameliorated Hcy-induced hepatic steatosis. The decrease in 
      hepatic lipid accumulation was mainly due to reduced hepatic levels of ceramides, 
      which was partly the result of the lower expression of ceramide synthesis genes, 
      Sptlc3 and Degs2. Similar beneficial effects of DHA were observed in 
      Hcy-stimulated primary hepatocytes in vitro. In summary, Hcy-induced ceramide 
      elevation in hepatocytes might contribute to the development of hepatic 
      steatosis. Furthermore, downregulation of ceramide levels through omega-3 PUFA 
      supplementation ameliorates hepatic lipid accumulation. Thus, ceramide is a 
      potential therapeutic target for the treatment of hepatic steatosis.
FAU - Dong, Yong-Qiang
AU  - Dong YQ
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry 
      of Education and Beijing Key Laboratory of Cardiovascular Receptors Research, 
      Beijing 100191, China.
FAU - Zhang, Xing-Zhong
AU  - Zhang XZ
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry 
      of Education and Beijing Key Laboratory of Cardiovascular Receptors Research, 
      Beijing 100191, China.
FAU - Sun, Lu-Lu
AU  - Sun LL
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry 
      of Education and Beijing Key Laboratory of Cardiovascular Receptors Research, 
      Beijing 100191, China.
FAU - Zhang, Song-Yang
AU  - Zhang SY
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry 
      of Education and Beijing Key Laboratory of Cardiovascular Receptors Research, 
      Beijing 100191, 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 and Beijing Key Laboratory of Cardiovascular Receptors Research, 
      Beijing 100191, China.
FAU - Liu, Hui-Ying
AU  - Liu HY
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry 
      of Education and Beijing Key Laboratory of Cardiovascular Receptors Research, 
      Beijing 100191, China.
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 and Beijing Key Laboratory of Cardiovascular Receptors Research, 
      Beijing 100191, China.
FAU - Jiang, Chang-Tao
AU  - Jiang CT
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry 
      of Education and Beijing Key Laboratory of Cardiovascular Receptors Research, 
      Beijing 100191, China.
LA  - eng
PT  - Journal Article
DEP - 20170921
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Ceramides)
RN  - 0 (Fatty Acids, Omega-3)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Ceramides/*biosynthesis
MH  - Fatty Acids, Omega-3/*pharmacology/*therapeutic use
MH  - Fatty Liver/*drug therapy/*etiology
MH  - Hepatocytes/*drug effects/metabolism
MH  - Hyperhomocysteinemia/*complications
MH  - Mice
MH  - Mice, Inbred C57BL
PMC - PMC5719150
EDAT- 2017/09/22 06:00
MHDA- 2018/07/24 06:00
PMCR- 2018/12/01
CRDT- 2017/09/22 06:00
PHST- 2017/04/12 00:00 [received]
PHST- 2017/08/01 00:00 [accepted]
PHST- 2017/09/22 06:00 [pubmed]
PHST- 2018/07/24 06:00 [medline]
PHST- 2017/09/22 06:00 [entrez]
PHST- 2018/12/01 00:00 [pmc-release]
AID - aps2017127 [pii]
AID - 10.1038/aps.2017.127 [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2017 Dec;38(12):1601-1610. doi: 10.1038/aps.2017.127. Epub 
      2017 Sep 21.