The Role of C-X-C motif chemokine 12 in the crosstalk of brown adipocytes and microvascular endothelial cells

Abstract

The pandemic of obesity keeps on rising. Especially from a pharmacological point of view, treatment options are quite limited. Late research has shown that brown adipose tissue might be a promising target for the development of innovative therapeutic strategies. However, biology of brown adipose tissue remains poorly understood. Utilizing in vitro assays, this study tackled the question whether microvascular endothelial cells and brown adipocytes potentially communicate via CXCL12. The data presented show that upon treatment with norepinephrine, brown adipocytes and microvascular endothelial cells release an increased amount of CXCL12. Further, it appears norepinephrine-stimulus induces hypoxia in brown adipose tissue. The data shown indicate that hypoxia yet again leads to an increase in CXCL12 released in both cell types, potentially mediated via HIF1a in microvascular endothelial cells and HIF2a in brown adipocytes. From a functional point of view, this work shows that CXCL12 leads to an increase in proliferation, tube formation and migration in microvascular endothelial cells, proposing CXCL12 plays a major role in angiogenesis in brown adipose tissue. Meanwhile, no evidence of CXCL12 interfering with brown adipocytes from a functional point of view was found. In summary, this work establishes a novel crosstalk of microvascular endothelial cells and brown adipocytes communicating via CXCL12, which potentially plays a vital role in (neo-)angiogenesis in brown adipose tissue.