PMID- 32208002
OWN - NLM
STAT- MEDLINE
DCOM- 20201026
LR  - 20240405
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 318
IP  - 6
DP  - 2020 Jun 1
TI  - GRP94 regulates M1 macrophage polarization and insulin resistance.
PG  - E1004-E1013
LID - 10.1152/ajpendo.00542.2019 [doi]
AB  - Macrophage polarization contributes to obesity-induced insulin resistance. 
      Glucose-regulated protein 94 (GRP94) is an endoplasmic reticulum (ER) chaperone 
      specialized for folding and quality control of secreted and membrane proteins. To 
      determine the role of GRP94 in macrophage polarization and insulin resistance, 
      macrophage-specific GRP94 conditional knockout (KO) mice were challenged with a 
      high-fat diet (HFD). Glucose tolerance, insulin sensitivity, and macrophage 
      composition were compared with control mice. KO mice showed better glucose 
      tolerance and increased insulin sensitivity. Adipose tissues from HFD-KO mice 
      contained lower numbers of M1 macrophages, with lower expression of M1 macrophage 
      markers, than wild-type (WT) mice. In vitro, WT adipocytes cocultured with KO 
      macrophages retained insulin sensitivity, whereas those cultured with WT 
      macrophages did not. In addition, compared with WT bone marrow-derived 
      macrophages (BMDMs), BMDMs from GRP94 KO mice exhibited lower expression of M1 
      macrophage marker genes following stimulation with LPS or IFN-gamma, and exhibited 
      partially increased expression of M2 macrophage marker genes following 
      stimulation with interleukin-4. These findings identify GRP94 as a novel 
      regulator of M1 macrophage polarization and insulin resistance and inflammation.
FAU - Song, Lili
AU  - Song L
AD  - State Key Laboratory of Agrobiotechnology, College of Biological Science, China 
      Agricultural University, Beijing, China.
AD  - Department of Surgery, Medical University of South Carolina, Charleston, South 
      Carolina.
FAU - Kim, Do-Sung
AU  - Kim DS
AD  - Department of Surgery, Medical University of South Carolina, Charleston, South 
      Carolina.
FAU - Gou, Wenyu
AU  - Gou W
AD  - Department of Surgery, Medical University of South Carolina, Charleston, South 
      Carolina.
FAU - Wang, Jingjing
AU  - Wang J
AD  - Department of Surgery, Medical University of South Carolina, Charleston, South 
      Carolina.
FAU - Wang, Ping
AU  - Wang P
AD  - Department of Surgery, Medical University of South Carolina, Charleston, South 
      Carolina.
FAU - Wei, Zhiguo
AU  - Wei Z
AD  - Department of Surgery, Medical University of South Carolina, Charleston, South 
      Carolina.
FAU - Liu, Bei
AU  - Liu B
AD  - Department of Medicine, Medical University of South Carolina, Charleston, South 
      Carolina.
FAU - Li, Zihai
AU  - Li Z
AD  - Department of Medicine, Medical University of South Carolina, Charleston, South 
      Carolina.
FAU - Gou, Kemian
AU  - Gou K
AD  - Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou 
      University, Yangzhou, China.
FAU - Wang, Hongjun
AU  - Wang H
AD  - Department of Surgery, Medical University of South Carolina, Charleston, South 
      Carolina.
AD  - Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina.
LA  - eng
GR  - P30 DK123704/DK/NIDDK NIH HHS/United States
GR  - R01 DK120394/DK/NIDDK NIH HHS/United States
GR  - P01 CA186866/CA/NCI NIH HHS/United States
GR  - R01 DK105183/DK/NIDDK NIH HHS/United States
GR  - R01 AI077283/AI/NIAID NIH HHS/United States
GR  - R01 DK118529/DK/NIDDK NIH HHS/United States
GR  - I01 BX004536/BX/BLRD VA/United States
GR  - R01 CA213290/CA/NCI NIH HHS/United States
GR  - R01 DK126454/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20200324
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (endoplasmin)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/metabolism
MH  - Animals
MH  - Coculture Techniques
MH  - Cytokines/genetics/immunology
MH  - *Diet, High-Fat
MH  - Glucose Tolerance Test
MH  - Inflammation/genetics/immunology
MH  - Insulin Resistance/*genetics/immunology
MH  - Interferon-gamma/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophage Activation/*genetics/immunology
MH  - Macrophages/drug effects/*immunology
MH  - Membrane Glycoproteins/*genetics/immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Obesity/genetics/*immunology/metabolism
MH  - RNA, Messenger/metabolism
PMC - PMC7311672
OTO - NOTNLM
OT  - GRP94
OT  - insulin sensitivity
OT  - macrophage polarization
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2020/03/26 06:00
MHDA- 2020/10/27 06:00
PMCR- 2021/06/01
CRDT- 2020/03/26 06:00
PHST- 2020/03/26 06:00 [pubmed]
PHST- 2020/10/27 06:00 [medline]
PHST- 2020/03/26 06:00 [entrez]
PHST- 2021/06/01 00:00 [pmc-release]
AID - E-00542-2019 [pii]
AID - 10.1152/ajpendo.00542.2019 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2020 Jun 1;318(6):E1004-E1013. doi: 
      10.1152/ajpendo.00542.2019. Epub 2020 Mar 24.