PMID- 30105954
OWN - NLM
STAT- MEDLINE
DCOM- 20190225
LR  - 20240330
IS  - 1535-3699 (Electronic)
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 243
IP  - 11
DP  - 2018 Jul
TI  - Nuclear factor erythroid 2-related factor 2 activation mediates 
      hyperhomocysteinemia-associated lipolysis suppression in adipocytes.
PG  - 926-933
LID - 10.1177/1535370218788520 [doi]
AB  - Hyperhomocysteinemia (HHcy) is associated with suppressed lipolytic response in 
      adipocytes/adipose tissue, however, the underlying mechanism remains to be 
      extensively studied. Nuclear factor erythroid 2-related factor 2 (Nrf2), a master 
      transcriptional factor regulating antioxidant generation, has been recently 
      reported to mediate lipid metabolism. Employing both fully differentiated 3T3-L1 
      adipocytes and male C57BL/6 mice, in the present study, we investigated the 
      potential involvement of Nrf2 activation in HHcy-mediated lipolytic suppression. 
      Our results showed that homocysteine (Hcy) treatment resulted in suppressed 
      lipolysis, evidenced by increased intracellular triglyceride (TG) accumulation, 
      decreased glycerol and free fatty acid (FFA) in fully differentiated 3T3-L1 
      adipocytes. Interestingly, Hcy exposure was associated with Nrf2 activation in 
      adipocytes. Further studies showed that Nrf2 knockdown via siRNA transfection 
      ameliorated Hcy-induced glycerol release in adipocytes. On the contrary, Nrf2 
      activators, epigallocatechin gallate (EGCG) and tert-butylhydroquinone (t-BHQ), 
      increased intracellular TG content and decreased glycerol release in adipocytes. 
      Importantly, our in vitro observations were corroborated by our in vivo findings, 
      in which Hcy feeding (0.1% wt/vol) for four weeks induced Nrf2 expression in 
      adipose tissue and lowered circulating FFA and glycerol levels in mice. 
      Furthermore, EGCG injection (5 mg/kg/d) decreased circulating glycerol levels in 
      comparison to the control group in mice. In conclusion, these results indicated 
      that Nrf2 activation in response to HHcy plays an important role in mediating 
      Hcy-suppressed lipolysis in adipocytes.
FAU - Li, Xin
AU  - Li X
AD  - 1 College of Medical Laboratory Science and Technology, Harbin Medical University 
      (Daqing), Daqing 163319, Heilongjiang, P. R. China.
FAU - Cheng, Yuhong
AU  - Cheng Y
AD  - 2 Daqing Medical College, Daqing 163312, Heilongjiang, P.R. China.
FAU - Zhong, Xiuli
AU  - Zhong X
AD  - 1 College of Medical Laboratory Science and Technology, Harbin Medical University 
      (Daqing), Daqing 163319, Heilongjiang, P. R. China.
FAU - Zhang, Bing
AU  - Zhang B
AD  - 1 College of Medical Laboratory Science and Technology, Harbin Medical University 
      (Daqing), Daqing 163319, Heilongjiang, P. R. China.
FAU - Bao, Zhiwei
AU  - Bao Z
AD  - 1 College of Medical Laboratory Science and Technology, Harbin Medical University 
      (Daqing), Daqing 163319, Heilongjiang, P. R. China.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - 1 College of Medical Laboratory Science and Technology, Harbin Medical University 
      (Daqing), Daqing 163319, Heilongjiang, P. R. China.
FAU - Wang, Zhigang
AU  - Wang Z
AD  - 1 College of Medical Laboratory Science and Technology, Harbin Medical University 
      (Daqing), Daqing 163319, Heilongjiang, P. R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (Fatty Acids)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 0 (Triglycerides)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - PDC6A3C0OX (Glycerol)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/drug effects/*metabolism
MH  - Animals
MH  - Cytoplasm/chemistry
MH  - Disease Models, Animal
MH  - Fatty Acids/analysis
MH  - Gene Knockdown Techniques
MH  - Glycerol/analysis
MH  - Homocysteine/metabolism
MH  - Hyperhomocysteinemia/*pathology
MH  - Lipolysis/*drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-E2-Related Factor 2/genetics/*metabolism
MH  - Triglycerides/analysis
PMC - PMC6108053
OTO - NOTNLM
OT  - 3T3-L1 adipocytes
OT  - Adipose
OT  - homocysteine
OT  - hyperhomocysteinemia
OT  - lipolysis
OT  - nuclear factor erythroid 2-related factor 2
EDAT- 2018/08/15 06:00
MHDA- 2019/02/26 06:00
PMCR- 2019/07/01
CRDT- 2018/08/15 06:00
PHST- 2018/08/15 06:00 [entrez]
PHST- 2018/08/15 06:00 [pubmed]
PHST- 2019/02/26 06:00 [medline]
PHST- 2019/07/01 00:00 [pmc-release]
AID - 10.1177_1535370218788520 [pii]
AID - 10.1177/1535370218788520 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2018 Jul;243(11):926-933. doi: 10.1177/1535370218788520.