Activation of CXCR7 exerts an inhibitory effect on adipogenesis through regulation of β-arrestin2/Wnt and AKT signalling.

Abstract

CXCR7, an alternative receptor for the inflammatory chemokine SDF-1, is involved in cell proliferation and migration. Recent studies have reported that CXCR7 also plays a role in adipose tissue. However, evidence regarding the role of CXCR7 and its ligands in adipocyte differentiation is limited. In this study, we aimed to elucidate changes in CXCR7 expression during adipocyte differentiation and the role of the SDF-1/CXCR7/CXCR4 axis in adipogenesis using recombinant SDF-1, the CXCR7 ligand CCX771, and small interfering RNAs. The results indicated that the levels of SDF-1 and its receptors, CXCR7 and CXCR4, decreased during the early stages of adipogenesis. Treatment with recombinant SDF-1 and CCX771 inhibited adipogenesis and lipid accumulation by inducing β-arrestin2, Wnt expression, and AKT phosphorylation and downregulating C/EBPα, PPARγ, and FABP4 expression. In contrast, knockdown of SDF-1 and CXCR7 in preadipocytes downregulated the β-arrestin2/Wnt and AKT pathway, leading to the induction of adipogenesis. Meanwhile, knockdown of CXCR4 had no significant effect. In mice, basal gene expression levels of SDF-1 and CXCR7 were higher in the stromal vascular fraction compared to mature adipocytes and were significantly upregulated by a high-fat diet. Our results provide new insights into the local role of the SDF-1-CXCR7 axis in adipocytes and offer additional benefits for the prevention of obesity-related metabolic disorders.