Presenting Author Auburn University Auburn, Alabama
Obesity is a multifactorial chronic condition that increases the risk of cardiovascular diseases, type II diabetes, and certain types of cancer. It has been known that some chemokines and their receptors facilitate the development of obesity, leading to other related comorbidities. However, the exact role of atypical chemokine receptor CXCR7 in obesity and obesity-induced type II diabetes remains unknown. We aimed to study whether CXCR7 promotes adipogenesis and insulin resistance in human visceral adipocytes in vitro. Using RT-PCR and flow cytometry studies, we found that both CXCR7 mRNA and its protein expressions were significantly upregulated during the differentiation of human visceral adipocytes. Stimulation of CXCR7 by SDF-1 or LIH383 (a CXCR7-selective peptide ligand) increased lipid droplets formation during adipocytes differentiation. In addition, we found that SDF-1 or LIH383 treatment inhibited AKT phosphorylation in a dose-dependent manner with no effect on ERK1/2 and JNK signaling pathways, which indicates a selective suppression of the AKT signaling axis by CXCR7. Furthermore, activation of CXCR7 by SDF-1 inhibited insulin signaling to the AKT pathway and insulin-induced glucose uptake. In contrast, ablation of CXCR7 by CRISPR/Cas9 system restored AKT signaling and enhanced insulin sensitivity in human visceral adipocytes. We concluded that CXCR7 plays a critical role in human visceral adipogenesis and insulin resistance by suppressing the AKT signaling pathway, highlighting CXCR7 as a potential new drug target against obesity and type II diabetes.
Support or Funding Information
Support in part by NIH funding 1R01HL125279-01A1 (to J.S.)
amp;nbsp;lt;span style="font-size: 12pt; font-family: amp;quot;Times New Romanamp;quot;, serif;"gt;Support in part by NIH funding 1R01HL125279-01A1 (to J.S.)lt;/spangt;
