PMID- 29341885
OWN - NLM
STAT- MEDLINE
DCOM- 20190423
LR  - 20240229
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Print)
IS  - 0303-7207 (Linking)
VI  - 473
DP  - 2018 Sep 15
TI  - Deletion of the Duffy antigen receptor for chemokines (DARC) promotes insulin 
      resistance and adipose tissue inflammation during high fat feeding.
PG  - 79-88
LID - S0303-7207(18)30015-7 [pii]
LID - 10.1016/j.mce.2018.01.006 [doi]
AB  - OBJECTIVE: Inflammation in adipose tissues in obesity promotes insulin resistance 
      and metabolic disease. The Duffy antigen receptor for chemokines (DARC) is a 
      promiscuous non-signaling receptor expressed on erythrocytes and other cell types 
      that modulates tissue inflammation by binding chemokines such as monocyte 
      chemoattractant protein-1 (MCP-1) and by acting as a chemokine reservoir. DARC 
      allelic variants are common in humans, but the role of DARC in modulating 
      obesity-related metabolic disease is unknown. METHODS: We examined body weight 
      gain, tissue adiposity, metabolic parameters and inflammatory marker expression 
      in wild-type and DARC knockout mice fed a chow diet (CD) and high fat diet (HFD). 
      RESULTS: Compared to wild-type mice, HFD-fed DARC knockout mice developed glucose 
      intolerance and insulin resistance independent of increases in body weight or 
      adiposity. Interestingly, insulin sensitivity was also diminished in lean male 
      DARC knockout mice fed a chow diet. Insulin production was not reduced by DARC 
      gene deletion, and plasma leptin levels were similar in HFD fed wild-type and 
      DARC knockout mice. MCP-1 levels in plasma rose significantly in the HFD fed 
      wild-type mice, but not in the DARC knockout mice. Conversely, adipose tissue 
      MCP-1 levels were higher, and more macrophage crown-like structures were 
      detected, in the HFD fed DARC knockout mice as compared with the wild-type mice, 
      consistent with augmented adipose tissue inflammation that is not accurately 
      reflected by plasma levels of DARC-bound MCP-1 in these mice. CONCLUSIONS: These 
      findings suggest that DARC regulates metabolic function and adipose tissue 
      inflammation, which may impact obesity-related disease in ethnic populations with 
      high frequencies of DARC allelic variants.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Benson, Tyler W
AU  - Benson TW
AD  - Vascular Biology Center, Medical College of Georgia at Augusta University, United 
      States.
FAU - Weintraub, Daniel S
AU  - Weintraub DS
AD  - Vascular Biology Center, Medical College of Georgia at Augusta University, United 
      States.
FAU - Crowe, Matthew
AU  - Crowe M
AD  - Vascular Biology Center, Medical College of Georgia at Augusta University, United 
      States.
FAU - Yiew, Nicole K H
AU  - Yiew NKH
AD  - Vascular Biology Center, Medical College of Georgia at Augusta University, United 
      States; Departments of Pharmacology and Toxicology, Medical College of Georgia at 
      Augusta University, United States.
FAU - Popoola, Orishebawo
AU  - Popoola O
AD  - Vascular Biology Center, Medical College of Georgia at Augusta University, United 
      States.
FAU - Pillai, Ajay
AU  - Pillai A
AD  - Vascular Biology Center, Medical College of Georgia at Augusta University, United 
      States.
FAU - Joseph, Joel
AU  - Joseph J
AD  - Vascular Biology Center, Medical College of Georgia at Augusta University, United 
      States.
FAU - Archer, Krystal
AU  - Archer K
AD  - Vascular Biology Center, Medical College of Georgia at Augusta University, United 
      States.
FAU - Greenway, Charlotte
AU  - Greenway C
AD  - Vascular Biology Center, Medical College of Georgia at Augusta University, United 
      States.
FAU - Chatterjee, Tapan K
AU  - Chatterjee TK
AD  - Vascular Biology Center, Medical College of Georgia at Augusta University, United 
      States.
FAU - Mintz, James
AU  - Mintz J
AD  - Vascular Biology Center, Medical College of Georgia at Augusta University, United 
      States.
FAU - Stepp, David W
AU  - Stepp DW
AD  - Vascular Biology Center, Medical College of Georgia at Augusta University, United 
      States; Physiology, Medical College of Georgia at Augusta University, United 
      States.
FAU - Stansfield, Brian K
AU  - Stansfield BK
AD  - Vascular Biology Center, Medical College of Georgia at Augusta University, United 
      States; Pediatrics, Medical College of Georgia at Augusta University, United 
      States.
FAU - Chen, Weiqin
AU  - Chen W
AD  - Physiology, Medical College of Georgia at Augusta University, United States.
FAU - Brittain, Julia
AU  - Brittain J
AD  - Vascular Biology Center, Medical College of Georgia at Augusta University, United 
      States; Cellular Biology and Anatomy, Medical College of Georgia at Augusta 
      University, United States.
FAU - Bogdanov, Vladimir Y
AU  - Bogdanov VY
AD  - Department of Medicine, University of Cincinnati College of Medicine, United 
      States.
FAU - Gao, Yan
AU  - Gao Y
AD  - Department of Physiology and Biophysics, University of Mississippi Medical 
      Center, United States.
FAU - Wilson, James G
AU  - Wilson JG
AD  - Department of Physiology and Biophysics, University of Mississippi Medical 
      Center, United States.
FAU - Tang, Yaoliang
AU  - Tang Y
AD  - Vascular Biology Center, Medical College of Georgia at Augusta University, United 
      States; Medicine, Medical College of Georgia at Augusta University, United 
      States.
FAU - Kim, Ha Won
AU  - Kim HW
AD  - Vascular Biology Center, Medical College of Georgia at Augusta University, United 
      States; Medicine, Medical College of Georgia at Augusta University, United 
      States. Electronic address: hkim3@augusta.edu.
FAU - Weintraub, Neal L
AU  - Weintraub NL
AD  - Vascular Biology Center, Medical College of Georgia at Augusta University, United 
      States; Medicine, Medical College of Georgia at Augusta University, United 
      States. Electronic address: nweintraub@augusta.edu.
LA  - eng
GR  - R01 HL126949/HL/NHLBI NIH HHS/United States
GR  - R01 HL112640/HL/NHLBI NIH HHS/United States
GR  - R01 DK093734/DK/NIDDK NIH HHS/United States
GR  - R01 AR070029/AR/NIAMS NIH HHS/United States
GR  - R01 HL086555/HL/NHLBI NIH HHS/United States
GR  - R01 HL134354/HL/NHLBI NIH HHS/United States
GR  - P20 GM121334/GM/NIGMS NIH HHS/United States
GR  - U54 GM115428/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20180116
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Duffy Blood-Group System)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Ackr1 protein mouse)
SB  - IM
MH  - Animals
MH  - Female
MH  - Male
MH  - *Adipose Tissue/pathology
MH  - Adiposity
MH  - *Diet, High-Fat
MH  - Duffy Blood-Group System/metabolism
MH  - *Feeding Behavior
MH  - *Gene Deletion
MH  - Glucose Intolerance/pathology
MH  - *Inflammation/pathology
MH  - *Insulin Resistance
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Phenotype
MH  - *Receptors, Cell Surface/deficiency/metabolism
MH  - Weight Gain
PMC - PMC6045443
MID - NIHMS941488
OTO - NOTNLM
OT  - DARC
OT  - High fat diet
OT  - Inflammation
OT  - Insulin resistance
OT  - Obesity
COIS- Conflicts of interest The authors declare no conflict of interest.
EDAT- 2018/01/18 06:00
MHDA- 2019/04/23 06:00
PMCR- 2018/09/15
CRDT- 2018/01/18 06:00
PHST- 2017/11/21 00:00 [received]
PHST- 2018/01/11 00:00 [revised]
PHST- 2018/01/12 00:00 [accepted]
PHST- 2018/01/18 06:00 [pubmed]
PHST- 2019/04/23 06:00 [medline]
PHST- 2018/01/18 06:00 [entrez]
PHST- 2018/09/15 00:00 [pmc-release]
AID - S0303-7207(18)30015-7 [pii]
AID - 10.1016/j.mce.2018.01.006 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2018 Sep 15;473:79-88. doi: 10.1016/j.mce.2018.01.006. Epub 
      2018 Jan 16.