CX3CL1-CX3CR1 Signaling Deficiency Exacerbates Obesity-induced Inflammation and Insulin Resistance in Male Mice.
Endocrinology
; 162(6)2021 06 01.
Article
em En
| MEDLINE
| ID: mdl-33765141
ABSTRACT
The CX3CL1-CX3CR1 system plays an important role in disease progression by regulating inflammation both positively and negatively. We reported previously that C-C chemokine receptors 2 and 5 promote obesity-associated adipose tissue inflammation and insulin resistance. Here, we demonstrate that CX3CL1-CX3CR1 signaling is involved in adipose tissue inflammation and insulin resistance in obese mice via adipose tissue macrophage recruitment and M1/M2 polarization. Cx3cl1 expression was persistently decreased in the epididymal white adipose tissue (eWAT) of high-fat diet-induced obese (DIO) mice, despite increased expression of other chemokines. Interestingly, in Cx3cr1-/- mice, glucose tolerance, insulin resistance, and hepatic steatosis induced by DIO or leptin deficiency were exacerbated. CX3CL1-CX3CR1 signaling deficiency resulted in reduced M2-polarized macrophage migration and an M1-dominant shift of macrophages within eWAT. Furthermore, transplantation of Cx3cr1-/- bone marrow was sufficient to impair glucose tolerance, insulin sensitivity, and regulation of M1/M2 status. Moreover, Cx3cl1 administration in vivo led to the attenuation of glucose intolerance and insulin resistance. Thus, therapy targeting the CX3CL1-CX3CR1 system may be beneficial in the treatment of type 2 diabetes by regulating M1/M2 macrophages.
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Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
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Quimiocina CX3CL1
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Receptor 1 de Quimiocina CX3C
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Inflamação
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Obesidade
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article