1. Functional analyses reveal the greater potency of preadipocytes compared with adipocytes as endothelial cell activator under normoxia, hypoxia, and TNFα exposure.
- Author
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Mack, Isabelle, BelAiba, Rachida S., Djordjevic, Talija, Görlach, Agnes, Hauner, Hans, and Bader, Bernhard L.
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FUNCTIONAL analysis ,FAT cells ,HYPOXEMIA ,TUMOR necrosis factors ,OBESITY ,ADIPOSE tissues ,CELL adhesion - Abstract
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 endotheha! cell activation have been neglected so far. To gain new insights into this molecular and cellular cross-talk, we examined the promflammatory expression and secretion of normoxia, hypoxia, and TNFa-treated human preadipocytes and adipocytes (SOBS 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 TNFa stimulation of SOBS 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. SOBS-CM upregulated the phosphorylation of three MAPK pathways, STAT1/3, and c-Jun in HMEC-1, whereas the NF-κB pathway was not affected. Inhibitor experiments showed that monocyte/endothelial cell-cell adhesion and endothelial ICAM-1 expression was JNK and JAK-1/STAT/3 pathway dependent and revealed IL-6 as a major mediator in CM increasing monocyte/endothelial cell-cell adhesion via the STAT 1/3 pathway. Our study shows that preadipocytes rather than adipocytes operate as potent activators of endothehial cells. This can be enhanced in preadipocytes and induced in adipocytes by TNFa and hypoxia in a manner similar to what may occur in WAT in the etiology of obesity. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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