P343	Inflammatory cytokines interleukin-6 and oncostatin M increase vascular endothelial growth factor in human adipose tissue.
1G.Rega, 1Chr.Kaun, 1T.Weiss, 1Ph.Hohensinner, 1S.Demyanets, 2R.Roehle, 3M.Frey, 1G.Maurer, 4K.Huber, 1J.Wojta
1Department of Internal Medicine II, Medical University Vienna, Vienna, AT; 2Department of Surgery, Wilhelminenspital, Vienna, AT; 3Department of Surgery, Medical University Vienna, Vienna, AT; 43rd Department of Medicine, Wilhelminenspital, Vienna, AT.

Background: Obesity is characterised by an increased adipose tissue mass with increased size and number of mature adipocytes. Recent studies suggest that adipose tissue mass could be regulated through the vasculature and differentiation of preadipocytes into adipocytes is angiogenesis dependent. Vascular endothelial growth factor (VEGF), a key agonist of angiogenesis is expressed and secreted by adipose tissue, but its regulation has been poorly examined. Elevated levels of the glycoprotein 130 (gp130) ligand interleukin-6 (IL-6) are found in obese patients. The aim of our study was to investigate whether the gp130 ligands IL-6, oncostatin M (OSM), leukemia inhibitory factor (LIF) and cardiotrophin-1 (CT-1) regulate VEGF expression in human visceral and subcutaneous adipose tissue in vitro and ex vivo. Methods: Primary human preadipocytes were prepared from visceral and subcutaneous adipose tissue. Differentiation to adipocytes was induced by hormone-supplementation. Explants of adipose tissue, preadipocytes and adipocytes were treated with IL-6 (100ng/ml), OSM (100ng/ml), LIF (104U/ml) and CT-1 (100ng/ml), respectively, for 48h. VEGF antigen in supernatants was quantified by ELISA, mRNA levels were determined by RealTimePCR. Results: IL-6 and OSM significantly upregulate VEGF production in both visceral and subcutaneous adipose tissue explants up to 2.5-fold (IL-6) and up to 9-fold and 6.5-fold (OSM), respectively. VEGF production is significantly upregulated in both preadipocytes and adipocytes up to 3-fold and 3.5-fold by IL-6, up to 7-fold and 15-fold by OSM and up to 3-fold and 1.5-fold by LIF. CT-1 upregulates VEGF only in visceral adipocytes (up to 3-fold). These results were confirmed on the level of mRNA expression. Conclusion: We could show that selected gp130 ligands significantly upregulate VEGF expression in human adipose tissue explants and in cultured human preadipocytes and adipocytes. We postulate that gp130 ligands participate in the modulation of VEGF synthesis in adipose tissue and we hypothesize, that high levels of circulating gp130 ligands such as IL-6 found in obese patients could promote angiogenesis in adipose tissue.

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