PMID- 33285413
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20240501
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 38
DP  - 2021 Jan
TI  - Increased Sirt1 secreted from visceral white adipose tissue is associated with 
      improved glucose tolerance in obese Nrf2-deficient mice.
PG  - 101805
LID - S2213-2317(20)31010-7 [pii]
LID - 10.1016/j.redox.2020.101805 [doi]
LID - 101805
AB  - Obesity is associated with metabolic dysregulation characterized by insulin 
      resistance and glucose intolerance. Nuclear factor E2-related factor (Nrf2) is a 
      critical regulator of the stress response and Nrf2-deficient mice (Nrf2(-/-)) are 
      protected against high fat diet (HFD)-induced metabolic derangement. We searched 
      for factors that could underline this favorable phenotype and found that 
      Nrf2(-/-) mice exhibit higher circulating levels of sirtuin 1 (Sirt1), a key 
      player in cellular homeostasis and energy metabolism, compared to wild-type mice. 
      Increased Sirt1 levels in Nrf2(-/-) mice were found not only in animals under 
      standard diet but also following HFD. Interestingly, we report here that the 
      visceral adipose tissue (eWAT) is the sole source of increased Sirt1 protein in 
      plasma. eWAT and other fat depots displayed enhanced adipocytes lipolysis, 
      increased fatty acid oxidation and glycolysis, suggesting autocrine and endocrine 
      actions of Sirt1 in this model. We further demonstrate that removal of eWAT 
      completely abolishes the increase in circulating Sirt1 and that this procedure 
      suppresses the beneficial effect of Nrf2 deficiency on glucose tolerance, but not 
      insulin sensitivity, following a HFD regime. Thus, in contrast to many other 
      stressful conditions where Nrf2 deficiency exacerbates damage, our study 
      indicates that up-regulation of Sirt1 levels specifically in the visceral adipose 
      tissue of Nrf2(-/-) mice is a key adaptive mechanism that mitigates glucose 
      intolerance induced by nutritional stress.
CI  - Copyright (c) 2020 The Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Braud, Laura
AU  - Braud L
AD  - University Paris-Est Creteil, INSERM, IMRB, F-94010, Creteil, France. Electronic 
      address: laura.braud@inserm.fr.
FAU - Pini, Maria
AU  - Pini M
AD  - University Paris-Est Creteil, INSERM, IMRB, F-94010, Creteil, France.
FAU - Stec, Donald F
AU  - Stec DF
AD  - Vanderbilt Institute for Chemical Biology (VICB), Vanderbilt University, 
      Nashville, USA.
FAU - Manin, Sylvie
AU  - Manin S
AD  - University Paris-Est Creteil, INSERM, IMRB, F-94010, Creteil, France.
FAU - Derumeaux, Genevieve
AU  - Derumeaux G
AD  - University Paris-Est Creteil, INSERM, IMRB, F-94010, Creteil, France.
FAU - Stec, David E
AU  - Stec DE
AD  - University of Mississippi Medical Center, Jackson, MS, 39216, USA.
FAU - Foresti, Roberta
AU  - Foresti R
AD  - University Paris-Est Creteil, INSERM, IMRB, F-94010, Creteil, France. Electronic 
      address: roberta.foresti@inserm.fr.
FAU - Motterlini, Roberto
AU  - Motterlini R
AD  - University Paris-Est Creteil, INSERM, IMRB, F-94010, Creteil, France. Electronic 
      address: roberto.motterlini@inserm.fr.
LA  - eng
GR  - P20 GM121334/GM/NIGMS NIH HHS/United States
GR  - R01 DK121748/DK/NIDDK NIH HHS/United States
GR  - S10 RR025677/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20201124
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
RN  - 0 (NF-E2-Related Factor 2)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adipose Tissue, White
MH  - Animals
MH  - Diet, High-Fat/adverse effects
MH  - Glucose
MH  - *Insulin Resistance/genetics
MH  - Intra-Abdominal Fat
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Obese
MH  - NF-E2-Related Factor 2/genetics
MH  - Obesity/genetics
MH  - *Sirtuin 1/genetics
PMC - PMC7721645
OTO - NOTNLM
OT  - Glucose metabolism
OT  - Nrf2
OT  - Obesity
OT  - Sirtuin 1
OT  - White adipose tissue
COIS- The authors declare no conflict of interest.
EDAT- 2020/12/08 06:00
MHDA- 2021/06/22 06:00
PMCR- 2020/11/24
CRDT- 2020/12/07 20:11
PHST- 2020/09/07 00:00 [received]
PHST- 2020/11/16 00:00 [revised]
PHST- 2020/11/18 00:00 [accepted]
PHST- 2020/12/08 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/12/07 20:11 [entrez]
PHST- 2020/11/24 00:00 [pmc-release]
AID - S2213-2317(20)31010-7 [pii]
AID - 101805 [pii]
AID - 10.1016/j.redox.2020.101805 [doi]
PST - ppublish
SO  - Redox Biol. 2021 Jan;38:101805. doi: 10.1016/j.redox.2020.101805. Epub 2020 Nov 
      24.