Vascular endothelial growth factor is induced by the inflammatory cytokines interleukin-6 and oncostatin m in human adipose tissue in vitro and in murine adipose tissue in vivo

Objectives - It is believed that adipose tissue acts as an endocrine organ by producing inflammatory mediators and thereby contributes to the increased cardiovascular risk seen in obesity. A link between adipose tissue mass and angiogenesis has been suggested. Vascular endothelial growth factor ( VEGF) seems to be implicated in this process. Members of the glycoprotein ( gp) 130 ligand family regulate VEGF expression in other cells. Methods and Results - We used tissue explants as well as primary cultures of preadipocytes and adipocytes from human subcutaneous and visceral adipose tissue to investigate whether the gp130 ligands oncostatin M ( OSM), interleukin- 6 ( IL- 6), leukemia inhibitory factor ( LIF), and cardiotrophin- 1 ( CT- 1) regulate VEGF expression in human adipose tissue. Human subcutaneous and visceral adipose tissue responded to treatment with IL- 6 and OSM with a significant increase in VEGF production. Human preadipocytes were isolated from subcutaneous and visceral adipose tissue. Adipocytedifferentiation was induced by hormone- supplementation. All cell types responded to IL- 6 and OSM with a robust increase in VEGF protein production and a similar increase in VEGF- specific mRNA. Furthermore, IL-1 beta synergistically enhanced the effect of OSM on VEGF production. AG- 490, a JAK/ STAT inhibitor, abolished the OSM-dependent VEGF induction almost completely. In mice, IL- 6 and OSM increased serum levels of VEGF and VEGF mRNA and vessel density in adipose tissue. Conclusion - We speculate that the inflammatory cytokines IL- 6 and OSM might support angiogenesis during adipose tissue growth by upregulating VEGF.