Endocrinology | 2021
CX3CL1-CX3CR1 signalling deficiency exacerbates obesity-induced inflammation and insulin resistance in male mice.
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 receptor 5, as well as CCR2, promotes obesity-associated adipose tissue inflammation and insulin resistance. Here, we demonstrate that CX3CL1-CX3CR1 signalling 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 \xa0-/- mice, glucose tolerance, insulin resistance, and hepatic steatosis induced by DIO or leptin deficiency were exacerbated. CX3CL1-CX3CR1 signalling deficiency resulted in reduced M2-polarized macrophage migration and an M1-dominant shift of macrophages within eWAT. Furthermore, transplantation of Cx3cr1 \xa0-/- 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.