Blocking CXCR7-mediated adipose tissue macrophages chemotaxis attenuates insulin resistance and inflammation in obesity.
Adipose tissue macrophages (ATMs) have been considered to have a pivotal role in the chronic inflammation development during obesity. Although chemokine-chemokine receptor interaction has been studied in ATMs infiltration, most chemokine receptors remain incompletely understood and little is known about their mechanism of actions that lead to ATMs chemotaxis and pathogenesis of insulin resistance during obesity. In this study, we reported that CXCR7 expression is upregulated in adipose tissue, and specifically in ATMs during obesity. In addition, CXCL11 or CXCL12-induced ATMs chemotaxis is mediated by CXCR7 in obesity but not leanness, whereas CXCR3 and CXCR4 are not involved. Additional mechanism study shows that NF-κB activation is essential in ATMs chemotaxis, and manipulates chemotaxis of ATMs via CXCR7 expression regulation in obesity. Most importantly, CXCR7 neutralizing therapy dose dependently leads to less infiltration of macrophages into adipose tissue and thus reduces inflammation and improves insulin sensitivity in obesity. In conclusion, these findings demonstrated that blocking CXCR7-mediated ATMs chemotaxis ameliorates insulin resistance and inflammation in obesity.
Department of Endocrinology, Shangqiu First People's Hospital, Shangqiu 476100, China. Electronic address: huiwushi@tom.com.
Hongxia
H
Peng
Department of Endocrinology, Shangqiu First People's Hospital, Shangqiu 476100, China.
Hu
H
Zhang
Health Center of Chengguan Town, Yucheng, Shangqiu 476300, China.
Honglei
H
Zhu
D000273:Adipose Tissue / Q000276:immunology*; D000818:Animals; D054371:Chemokine CXCL11 / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D007333:Insulin Resistance / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000097:blood; D054387:Receptors, CXCR / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D000097782:NF-kappaB-Inducing Kinase
D054371:Chemokine CXCL11; D054377:Chemokine CXCL12; D017346:Protein Serine-Threonine Kinases; D054387:Receptors, CXCR; D000097782:NF-kappaB-Inducing Kinase; C501897:Cmkor1 protein, mouse; C515203:Cxcl11 protein, mouse; C515256:Cxcl12 protein, mouse
CXCR7; Chemotaxis; Inflammation; Insulin resistance; Obesity