PMID- 35806422
OWN - NLM
STAT- MEDLINE
DCOM- 20220712
LR  - 20230401
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 13
DP  - 2022 Jul 3
TI  - An Iron Refractory Phenotype in Obese Adipose Tissue Macrophages Leads to 
      Adipocyte Iron Overload.
LID - 10.3390/ijms23137417 [doi]
LID - 7417
AB  - Adipocyte iron overload is a maladaptation associated with obesity and insulin 
      resistance. The objective of the current study was to determine whether and how 
      adipose tissue macrophages (ATMs) regulate adipocyte iron concentrations and 
      whether this is impacted by obesity. Using bone marrow-derived macrophages 
      (BMDMs) polarized to M0, M1, M2, or metabolically activated (MMe) phenotypes, we 
      showed that MMe BMDMs and ATMs from obese mice have reduced expression of several 
      iron-related proteins. Furthermore, the bioenergetic response to iron in obese 
      ATMs was hampered. ATMs from iron-injected lean mice increased their glycolytic 
      and respiratory capacities, thus maintaining metabolic flexibility, while ATMs 
      from obese mice did not. Using an isotope-based system, we found that iron 
      exchange between BMDMs and adipocytes was regulated by macrophage phenotype. At 
      the end of the co-culture, MMe macrophages transferred and received more iron 
      from adipocytes than M0, M1, and M2 macrophages. This culminated in a decrease in 
      total iron in MMe macrophages and an increase in total iron in adipocytes 
      compared with M2 macrophages. Taken together, in the MMe condition, the 
      redistribution of iron is biased toward macrophage iron deficiency and 
      simultaneous adipocyte iron overload. These data suggest that obesity changes the 
      communication of iron between adipocytes and macrophages and that rectifying this 
      iron communication channel may be a novel therapeutic target to alleviate insulin 
      resistance.
FAU - Ameka, Magdalene K
AU  - Ameka MK
AD  - Department of Molecular Physiology and Biophysics, School of Medicine, Vanderbilt 
      University, Nashville, TN 37212, USA.
FAU - Beavers, William N
AU  - Beavers WN
AD  - Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana 
      State University, Baton Rouge, LA 70803, USA.
FAU - Shaver, Ciara M
AU  - Shaver CM
AD  - Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University 
      Medical Center, Nashville, TN 37212, USA.
FAU - Ware, Lorraine B
AU  - Ware LB
AUID- ORCID: 0000-0002-9429-4702
AD  - Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University 
      Medical Center, Nashville, TN 37212, USA.
AD  - Department of Pathology, Microbiology, and Immunology, School of Medicine, 
      Vanderbilt University Medical Center, Nashville, TN 37212, USA.
FAU - Kerchberger, Vern Eric
AU  - Kerchberger VE
AUID- ORCID: 0000-0002-0342-1965
AD  - Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University 
      Medical Center, Nashville, TN 37212, USA.
AD  - Department of Pathology, Microbiology, and Immunology, School of Medicine, 
      Vanderbilt University Medical Center, Nashville, TN 37212, USA.
FAU - Schoenfelt, Kelly Q
AU  - Schoenfelt KQ
AD  - Department of Cancer Research, University of Chicago, Chicago, IL 60637, USA.
FAU - Sun, Lili
AU  - Sun L
AD  - Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 
      37212, USA.
FAU - Koyama, Tatsuki
AU  - Koyama T
AUID- ORCID: 0000-0002-8908-9165
AD  - Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 
      37212, USA.
FAU - Skaar, Eric P
AU  - Skaar EP
AD  - Department of Pathology, Microbiology, and Immunology, School of Medicine, 
      Vanderbilt University Medical Center, Nashville, TN 37212, USA.
FAU - Becker, Lev
AU  - Becker L
AD  - Department of Cancer Research, University of Chicago, Chicago, IL 60637, USA.
FAU - Hasty, Alyssa H
AU  - Hasty AH
AUID- ORCID: 0000-0001-7302-8045
AD  - Department of Molecular Physiology and Biophysics, School of Medicine, Vanderbilt 
      University, Nashville, TN 37212, USA.
AD  - VA Tennessee Valley Healthcare System, Nashville, TN 37212, USA.
LA  - eng
GR  - 20POST35180180/American Heart Association/
GR  - R01 DK121520/DK/NIDDK NIH HHS/United States
GR  - DK058404/DK/NIDDK NIH HHS/United States
GR  - P30 DK058404/DK/NIDDK NIH HHS/United States
GR  - DK102960/DK/NIDDK NIH HHS/United States
GR  - CA68485/CA/NCI NIH HHS/United States
GR  - K08 HL136888/HL/NHLBI NIH HHS/United States
GR  - 18POST34030426/American Heart Association/
GR  - K01 HL157755/HL/NHLBI NIH HHS/United States
GR  - HL136888/National Heart Lung and Blood Institute/
GR  - R01 DK102960/DK/NIDDK NIH HHS/United States
GR  - DK121520/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20220703
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Adipocytes/metabolism
MH  - Adipose Tissue/metabolism
MH  - Animals
MH  - Inflammation/metabolism
MH  - *Insulin Resistance
MH  - Iron/metabolism
MH  - *Iron Overload/metabolism
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Obese
MH  - Obesity/metabolism
MH  - Phenotype
PMC - PMC9267114
OTO - NOTNLM
OT  - adipose tissue macrophage
OT  - immunometabolism
OT  - iron
OT  - obesity
OT  - polarization
COIS- The authors declare no conflict of interest.
EDAT- 2022/07/10 06:00
MHDA- 2022/07/14 06:00
PMCR- 2022/07/03
CRDT- 2022/07/09 01:13
PHST- 2022/06/09 00:00 [received]
PHST- 2022/06/30 00:00 [revised]
PHST- 2022/07/01 00:00 [accepted]
PHST- 2022/07/09 01:13 [entrez]
PHST- 2022/07/10 06:00 [pubmed]
PHST- 2022/07/14 06:00 [medline]
PHST- 2022/07/03 00:00 [pmc-release]
AID - ijms23137417 [pii]
AID - ijms-23-07417 [pii]
AID - 10.3390/ijms23137417 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Jul 3;23(13):7417. doi: 10.3390/ijms23137417.