PMID- 31931283
OWN - NLM
STAT- MEDLINE
DCOM- 20210416
LR  - 20210423
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 30
DP  - 2020 Feb
TI  - Long isoforms of NRF1 negatively regulate adipogenesis via suppression of PPARgamma 
      expression.
PG  - 101414
LID - S2213-2317(19)31051-1 [pii]
LID - 10.1016/j.redox.2019.101414 [doi]
LID - 101414
AB  - Nuclear factor erythroid 2-related factor 1 (NRF1), a ubiquitously expressed 
      CNC-bZIP transcription factor, plays a critical role in white adipocyte (WAC) 
      biology, whereas the underlying mechanisms remain unknown. The mouse Nrf1 gene is 
      transcribed in a number of alternatively spliced forms, resulting in two long 
      protein isoforms (L-NRF1) containing 741 and 742 amino acids (aa) and multiple 
      short isoforms (S-NRF1). Our previous study found that adipocyte-specific 
      knockout of Nrf1 [Nrf1(f)-KO] in mice disturbs the expression of lipolytic genes 
      in adipocytes, leading to adipocyte hypertrophy followed by inflammation, 
      pyroptosis and insulin resistance. In the present study, we found that the 
      stromal vascular fraction (SVF) cells isolated from white adipose tissues (WAT) 
      of Nrf1(f)-KO mice display augmented adipogenesis showing elevated mRNA and 
      protein expression of adipogenic markers and lipid accumulation. In 3T3-L1 cells, 
      stable knockdown (KD) of all or long isoforms of Nrf1 (termed as A-Nrf1-KD and 
      L-Nrf1-KD, respectively) using lentiviral shRNAs resulted in enhanced and 
      accelerated adipogenic differentiation. Conversely, overexpression of L-NRF1-741, 
      but not any of the S-NRF1, substantially attenuated adipogenesis in 3T3-L1 cells. 
      These findings indicate that L-NRF1 might serve as a critical negative regulator 
      of adipogenesis. Mechanistic investigation revealed that L-NRF1 may negatively 
      regulates the transcription of peroxisome proliferator-activated receptor gamma 
      (PPARgamma), in particular the master regulator of adipogenesis PPARgamma2. Taken all 
      together, the findings in the present study provide further evidence for a novel 
      role of NRF1 beyond its participation in cellular antioxidant response and 
      suggest that L-NRF1 is a negative regulator of PPARgamma2 expression and thereby can 
      suppress adipogenesis.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Xue, Peng
AU  - Xue P
AD  - School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang 
      North New Area, Shenyang, Liaoning, 110122, PR China; ScitoVation LLC, Research 
      Triangle Park, NC, USA.
FAU - Hou, Yongyong
AU  - Hou Y
AD  - School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang 
      North New Area, Shenyang, Liaoning, 110122, PR China.
FAU - Zuo, Zhuo
AU  - Zuo Z
AD  - School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang 
      North New Area, Shenyang, Liaoning, 110122, PR China.
FAU - Wang, Zhendi
AU  - Wang Z
AD  - School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang 
      North New Area, Shenyang, Liaoning, 110122, PR China.
FAU - Ren, Suping
AU  - Ren S
AD  - School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang 
      North New Area, Shenyang, Liaoning, 110122, PR China.
FAU - Dong, Jian
AU  - Dong J
AD  - ScitoVation LLC, Research Triangle Park, NC, USA.
FAU - Fu, Jingqi
AU  - Fu J
AD  - School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang 
      North New Area, Shenyang, Liaoning, 110122, PR China.
FAU - Wang, Huihui
AU  - Wang H
AD  - School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang 
      North New Area, Shenyang, Liaoning, 110122, PR China.
FAU - Andersen, Melvin E
AU  - Andersen ME
AD  - ScitoVation LLC, Research Triangle Park, NC, USA.
FAU - Zhang, Qiang
AU  - Zhang Q
AD  - Department of Environmental Health, Rollins School of Public Health, Emory 
      University, Atlanta, GA, USA.
FAU - Xu, Yuanyuan
AU  - Xu Y
AD  - School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang 
      North New Area, Shenyang, Liaoning, 110122, PR China. Electronic address: 
      yyxu@cmu.edu.cn.
FAU - Pi, Jingbo
AU  - Pi J
AD  - School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang 
      North New Area, Shenyang, Liaoning, 110122, PR China. Electronic address: 
      jbpi@cmu.edu.cn.
LA  - eng
GR  - P30 ES019776/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191228
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
RN  - 0 (NF-E2-Related Factor 1)
RN  - 0 (Nfe2L1 protein, mouse)
RN  - 0 (PPAR gamma)
RN  - 0 (Pparg protein, mouse)
RN  - 0 (Protein Isoforms)
SB  - IM
MH  - 3T3-L1 Cells
MH  - *Adipogenesis
MH  - Animals
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Female
MH  - Gene Knockout Techniques
MH  - Male
MH  - Mice
MH  - NF-E2-Related Factor 1/*genetics/*metabolism
MH  - PPAR gamma/*genetics/*metabolism
MH  - Promoter Regions, Genetic
MH  - Protein Isoforms/genetics/metabolism
PMC - PMC6957832
OTO - NOTNLM
OT  - Adipogenesis
OT  - NRF1
OT  - PPARgamma
OT  - White adipocytes
COIS- Declaration of competing interest The authors have no conflicts of interest to 
      disclose.
EDAT- 2020/01/14 06:00
MHDA- 2021/04/17 06:00
PMCR- 2019/12/28
CRDT- 2020/01/14 06:00
PHST- 2019/09/06 00:00 [received]
PHST- 2019/12/02 00:00 [revised]
PHST- 2019/12/23 00:00 [accepted]
PHST- 2020/01/14 06:00 [pubmed]
PHST- 2021/04/17 06:00 [medline]
PHST- 2020/01/14 06:00 [entrez]
PHST- 2019/12/28 00:00 [pmc-release]
AID - S2213-2317(19)31051-1 [pii]
AID - 101414 [pii]
AID - 10.1016/j.redox.2019.101414 [doi]
PST - ppublish
SO  - Redox Biol. 2020 Feb;30:101414. doi: 10.1016/j.redox.2019.101414. Epub 2019 Dec 
      28.