Functional analyses reveal the greater potency of preadipocytes compared with adipocytes as endothelial cell activator under normoxia, hypoxia, and TNFalpha exposure.
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 TNFalpha-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 TNFalpha 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-kappaB 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 TNFalpha and hypoxia in a manner similar to what may occur in WAT in the etiology of obesity.
Mack
Isabelle
I
Dept. of Nutritional Medicine, Else Kröner-Fresenius-Center for Nutritional Medicine, Technische Universität München, D-85350 Freising Weihenstephan, Germany.
BelAiba
Rachida S
RS
Djordjevic
Talija
T
Görlach
Agnes
A
Hauner
Hans
H
Bader
Bernhard L
BL
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D000072000:NF-KappaB Inhibitor alpha; D010100:Oxygen / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D020298:U937 Cells
D017077:Culture Media, Conditioned; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; C000606204:NFKBIA protein, human; C498143:RELA protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D010100:Oxygen