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This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/E735    most recent 90851.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Mack, I. Articles by Bader, B. L. PubMed PubMed Citation Articles by Mack, I. Articles by Bader, B. L.

Functional analyses reveal the greater potency of preadipocytes compared with adipocytes as endothelial cell activator under normoxia, hypoxia, and TNF exposure

¹Department of Nutritional Medicine, Else Kröner-Fresenius-Center for Nutritional Medicine, Technische Universität München, Freising Weihenstephan; and ²Experimental Pediatric Cardiology, Department of Pediatric Cardiology and Congenital Heart Disease, German Heart Center Munich, Technische Universität München, Munich, Germany

Submitted 20 October 2008 ; accepted in final form 18 June 2009

Obesity is associated with a state of chronic low-grade inflammation. Immune cells accumulate in white adipose tissue (WAT). The vascular endothelium plays an interactive role in these infiltration and inflammatory processes. Mature and hypertrophic adipocytes are considered as the major adipogenic cell type secreting proinflammatory cytokines in WAT. In contrast, the proinflammatory capacity of preadipocytes and their role in endothelial cell activation have been neglected so far. To gain new insights into this molecular and cellular cross-talk, we examined the proinflammatory expression and secretion of normoxia, hypoxia, and TNF-treated human preadipocytes and adipocytes (SGBS cells) and their impact on human microvascular endothelial cell (HMEC-1) function. In this study, stimulation of HMEC-1 with conditioned media (CM) from preadipocytes increased endothelial ICAM-1 expression and monocyte adhesion but not adipocyte-CM. After hypoxia and TNF stimulation of SGBS cells, adipocyte-CM induced and preadipocyte-CM enhanced the monocyte adhesion. Concordantly, the expression of proinflammatory adipokines was considerably higher in preadipocytes than in adipocytes. SGBS-CM upregulated the phosphorylation of three MAPK pathways, STAT1/3, and c-Jun in HMEC-1, whereas the NF-B pathway was not affected. Inhibitor experiments showed that monocyte/endothelial cell-cell adhesion and endothelial ICAM-1 expression was JNK and JAK-1/STAT1/3 pathway dependent and revealed IL-6 as a major mediator in CM increasing monocyte/endothelial cell-cell adhesion via the STAT1/3 pathway. Our study shows that preadipocytes rather than adipocytes operate as potent activators of endothelial cells. This can be enhanced in preadipocytes and induced in adipocytes by TNF and hypoxia in a manner similar to what may occur in WAT in the etiology of obesity.

tumor necrosis factor-; human interleukin-6; adipokine; obesity; inflammation; signaling