Functional analyses reveal the greater potency of preadipocytes compared with adipocytes as endothelial cell activator under normoxia, hypoxia, and TNFα exposure
Functional analyses reveal the greater potency of preadipocytes compared with adipocytes as endothelial cell activator under normoxia, hypoxia, and TNFα exposure
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DOI：
10.1152/ajpendo.90851.2008
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发表时间：
2009-09-01
影响因子：
5.1
通讯作者：
Bader, Bernhard L.
中科院分区：
文献类型：
--
作者：
Mack, Isabelle;BelAiba, Rachida S.;Bader, Bernhard L.
Mack I，BelAiba RS，Djordjevic T，Gorlach A，Hauner H，Bader BL.功能分析显示，与脂肪细胞相比，前脂肪细胞在常氧、缺氧和TNF α暴露下作为内皮细胞激活剂的效力更大。Am J Physiol Endocrinol Metab 297：E735-E748，2009.首次发表于2009年6月23日; doi：10.1152/ajpendo.90851.2008。肥胖与慢性低度炎症状态有关。免疫细胞在白色脂肪组织（WAT）中积累。血管内皮在这些浸润和炎症过程中起着相互作用。成熟和肥大脂肪细胞被认为是WAT中分泌促炎细胞因子的主要成脂细胞类型。相比之下，前脂肪细胞的促炎能力和它们在内皮细胞活化中的作用至今被忽视。为了获得对这种分子和细胞串扰的新见解，我们研究了常氧、缺氧和TNF α处理的人前脂肪细胞和脂肪细胞（SGBS细胞）的促炎表达和分泌及其对人微血管内皮细胞（HMEC-1）功能的影响。在这项研究中，刺激HMEC-1与条件培养基（CM）从前脂肪细胞增加内皮细胞ICAM-1的表达和单核细胞粘附，但不是脂肪细胞-CM。SGBS细胞经缺氧和TNF α刺激后，脂肪细胞-CM诱导单核细胞粘附，前脂肪细胞-CM增强单核细胞粘附。一致地，促炎性脂肪因子的表达在前脂肪细胞中比在脂肪细胞中高得多。SGBS-CM可上调HMEC-1中三条MAPK通路STAT 1/3和c-Jun的磷酸化，而NF-κ B通路不受影响。抑制剂实验表明，单核细胞/内皮细胞-细胞粘附和内皮细胞ICAM-1表达是JNK和JAK-1/STAT 1/3途径依赖性的，并揭示IL-6作为CM的主要介质通过STAT 1/3途径增加单核细胞/内皮细胞-细胞粘附。我们的研究表明，前脂肪细胞，而不是脂肪细胞作为有效的激活剂的内皮细胞。这可以在前脂肪细胞中增强，并通过TNF α和缺氧在脂肪细胞中诱导，其方式类似于肥胖病因学中可能发生在WAT中的方式。
Mack I, BelAiba RS, Djordjevic T, Gorlach A, Hauner H, Bader BL. Functional analyses reveal the greater potency of preadipocytes compared with adipocytes as endothelial cell activator under normoxia, hypoxia, and TNF alpha exposure. Am J Physiol Endocrinol Metab 297: E735-E748, 2009. First published June 23, 2009; doi: 10.1152/ajpendo.90851.2008.-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 alpha-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 alpha 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-kappa 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 alpha and hypoxia in a manner similar to what may occur in WAT in the etiology of obesity.