Deletion of the Duffy antigen receptor for chemokines (DARC) promotes insulin resistance and adipose tissue inflammation during high fat feeding

Tyler W. Benson, Daniel S. Weintraub, Matthew Crowe, Nicole K.H. Yiew, Orishebawo Popoola, Ajay Pillai, Joel Joseph, Krystal Archer, Charlotte Greenway, Tapan K. Chatterjee, James Mintz, David W Stepp, Brian Kevin Stansfield, Weiqin Chen, Julia Brittain, Vladimir Y. Bogdanov, Yan Gao, James G. Wilson, Yao Liang Tang, Ha Won Kim & 1 others Neal Lee Weintraub

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)79-88
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume473
DOIs
StatePublished - Sep 15 2018

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Antigen Receptors
Chemokines
Insulin Resistance
Adipose Tissue
Fats
Insulin
Tissue
Inflammation
Nutrition
Knockout Mice
High Fat Diet
Chemokine CCL2
Obesity
Metabolic Diseases
Adiposity
Plasmas
Body Weight
Diet
Glucose Intolerance
Gene Deletion

Keywords

  • DARC
  • High fat diet
  • Inflammation
  • Insulin resistance
  • Obesity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

Deletion of the Duffy antigen receptor for chemokines (DARC) promotes insulin resistance and adipose tissue inflammation during high fat feeding. / Benson, Tyler W.; Weintraub, Daniel S.; Crowe, Matthew; Yiew, Nicole K.H.; Popoola, Orishebawo; Pillai, Ajay; Joseph, Joel; Archer, Krystal; Greenway, Charlotte; Chatterjee, Tapan K.; Mintz, James; Stepp, David W; Stansfield, Brian Kevin; Chen, Weiqin; Brittain, Julia; Bogdanov, Vladimir Y.; Gao, Yan; Wilson, James G.; Tang, Yao Liang; Kim, Ha Won; Weintraub, Neal Lee.

In: Molecular and Cellular Endocrinology, Vol. 473, 15.09.2018, p. 79-88.

Research output: Contribution to journalArticle

Benson, TW, Weintraub, DS, Crowe, M, Yiew, NKH, Popoola, O, Pillai, A, Joseph, J, Archer, K, Greenway, C, Chatterjee, TK, Mintz, J, Stepp, DW, Stansfield, BK, Chen, W, Brittain, J, Bogdanov, VY, Gao, Y, Wilson, JG, Tang, YL, Kim, HW & Weintraub, NL 2018, 'Deletion of the Duffy antigen receptor for chemokines (DARC) promotes insulin resistance and adipose tissue inflammation during high fat feeding', Molecular and Cellular Endocrinology, vol. 473, pp. 79-88. https://doi.org/10.1016/j.mce.2018.01.006
Benson, Tyler W. ; Weintraub, Daniel S. ; Crowe, Matthew ; Yiew, Nicole K.H. ; Popoola, Orishebawo ; Pillai, Ajay ; Joseph, Joel ; Archer, Krystal ; Greenway, Charlotte ; Chatterjee, Tapan K. ; Mintz, James ; Stepp, David W ; Stansfield, Brian Kevin ; Chen, Weiqin ; Brittain, Julia ; Bogdanov, Vladimir Y. ; Gao, Yan ; Wilson, James G. ; Tang, Yao Liang ; Kim, Ha Won ; Weintraub, Neal Lee. / Deletion of the Duffy antigen receptor for chemokines (DARC) promotes insulin resistance and adipose tissue inflammation during high fat feeding. In: Molecular and Cellular Endocrinology. 2018 ; Vol. 473. pp. 79-88.
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abstract = "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.",
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T1 - Deletion of the Duffy antigen receptor for chemokines (DARC) promotes insulin resistance and adipose tissue inflammation during high fat feeding

AU - Benson, Tyler W.

AU - Weintraub, Daniel S.

AU - Crowe, Matthew

AU - Yiew, Nicole K.H.

AU - Popoola, Orishebawo

AU - Pillai, Ajay

AU - Joseph, Joel

AU - Archer, Krystal

AU - Greenway, Charlotte

AU - Chatterjee, Tapan K.

AU - Mintz, James

AU - Stepp, David W

AU - Stansfield, Brian Kevin

AU - Chen, Weiqin

AU - Brittain, Julia

AU - Bogdanov, Vladimir Y.

AU - Gao, Yan

AU - Wilson, James G.

AU - Tang, Yao Liang

AU - Kim, Ha Won

AU - Weintraub, Neal Lee

PY - 2018/9/15

Y1 - 2018/9/15

N2 - 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.

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KW - DARC

KW - High fat diet

KW - Inflammation

KW - Insulin resistance

KW - Obesity

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