PMID- 34405211
OWN - NLM
STAT- MEDLINE
DCOM- 20210819
LR  - 20210819
IS  - 0371-0874 (Print)
IS  - 0371-0874 (Linking)
VI  - 73
IP  - 4
DP  - 2021 Aug 25
TI  - [n-3 Polyunsaturated fatty acid attenuates hyperhomocysteinemia-induced hepatic 
      steatosis by increasing hepatic LXA(5) content].
PG  - 551-558
AB  - Nonalcoholic fatty liver disease (NAFLD) and hyperhomocysteinemia (HHcy) both are 
      major health problems worldwide, whose incidence are closely related with each 
      other. We previously reported the mechanism of HHcy-caused hepatic steatosis, but 
      the role of n-3 polyunsaturated fatty acid (n-3 PUFA) in HHcy-induced hepatic 
      steatosis remains unclear. In this study, 6-week-old C57BL/6 male mice were given 
      a high methionine diet (HMD, 2% methionine diet), and plasma homocysteine levels 
      were measured by ELISA to confirm the establishment of an HHcy model. Meantime, 
      mice were fed HMD with or without n-3 PUFA supplement for 8 weeks to determine 
      the role and mechanism of n-3 PUFA in hepatic steatosis induced by HHcy. Results 
      showed that n-3 PUFA significantly improved hepatic lipid deposition induced by 
      HHcy. qRT-PCR analysis demonstrated that n-3 PUFA inhibited the upregulation of 
      Cd36, a key enzyme of fatty acid uptake, caused by HHcy. Further, the inhibition 
      of hepatic Cd36 expression was associated with the inactivation of aryl 
      hydrocarbon receptor (Ahr) induced by n-3 PUFA. Of note, mass spectrometry 
      revealed that hepatic content of lipoxin A(5) (LXA(5)) was significantly 
      increased in HMD+n-3 PUFA-fed mice compared with that in HMD-fed mice. In primary 
      cultured hepatocytes, LXA(5) treatment markedly reversed homocysteine-evoked Cd36 
      upregulation and Ahr activation, which resulted in reduced lipid accumulation. In 
      conclusion, we demonstrate that n-3 PUFA inactivates HHcy-induced Ahr-Cd36 
      pathway by increasing hepatic LXA(5) content, which alleviates hepatic steatosis. 
      Thus, our results may provide a potential strategy for treatment of NAFLD.
FAU - Song, Hao
AU  - Song H
AD  - Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 
      300070, China.
FAU - Duan, Jin-Jie
AU  - Duan JJ
AD  - Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 
      300070, China.
FAU - Li, Kan
AU  - Li K
AD  - Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 
      300070, China.
FAU - Yao, Liu
AU  - Yao L
AD  - Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 
      300070, China. yaoliu@tmu.edu.cn.
FAU - Zhu, Yi
AU  - Zhu Y
AD  - Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 
      300070, China.
LA  - chi
PT  - Journal Article
PL  - China
TA  - Sheng Li Xue Bao
JT  - Sheng li xue bao : [Acta physiologica Sinica]
JID - 20730130R
RN  - 0 (Fatty Acids, Omega-3)
SB  - IM
MH  - Animals
MH  - *Fatty Acids, Omega-3
MH  - *Fatty Liver/drug therapy
MH  - *Hyperhomocysteinemia/complications/drug therapy
MH  - Liver
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
EDAT- 2021/08/19 06:00
MHDA- 2021/08/20 06:00
CRDT- 2021/08/18 06:33
PHST- 2021/08/18 06:33 [entrez]
PHST- 2021/08/19 06:00 [pubmed]
PHST- 2021/08/20 06:00 [medline]
PST - ppublish
SO  - Sheng Li Xue Bao. 2021 Aug 25;73(4):551-558.