Immune cell-derived cytokines contribute to obesity-related inflammation, fibrogenesis and metabolic deregulation in human adipose tissue

被引：99
作者：
Caer, Charles [1 ,2 ,3 ]
Rouault, Christine [1 ,2 ,3 ]
Le Roy, Tiphaine [1 ,2 ,3 ]
Poitou, Christine [1 ,2 ,3 ,4 ]
Aron-Wisnewsky, Judith [1 ,2 ,3 ,4 ]
Torcivia, Adriana [5 ]
Bichet, Jean-Christophe [6 ]
Clement, Karine [1 ,2 ,3 ,4 ]
Guerre-Millo, Michele [1 ,2 ,3 ]
Andre, Sebastien [1 ,2 ,3 ]
机构：
[1] INSERM, UMR S 1166, Team Nutri 6, F-75013 Paris, France
[2] UPMC Univ Paris 06, Sorbonne Univ, UMR S 1166, F-75005 Paris, France
[3] Hop La Pitie Salpetriere, AP HP, ICAN, F-75013 Paris, France
[4] Hop La Pitie Salpetriere, AP HP, Nutr & Endocrinol Dept, F-75013 Paris, France
[5] Hop La Pitie Salpetriere, AP HP, Hepatobiliary & Digest Surg Dept, F-75013 Paris, France
[6] Hop La Pitie Salpetriere, AP HP, Plast Surg & Mammary Canc Dept, F-75013 Paris, France
来源：
SCIENTIFIC REPORTS | 2017年 / 7卷
关键词：
NECROSIS-FACTOR-ALPHA; INSULIN-RESISTANCE; ADIPOCYTES; IL-17; INTERLEUKIN-6; ADIPOGENESIS; EXPRESSION; FIBROSIS; KERATINOCYTES; SECRETION;
D O I：
10.1038/s41598-017-02660-w
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Adipose tissue contains a variety of immune cells, which vary in abundance and phenotype with obesity. The contribution of immune cell-derived factors to inflammatory, fibrotic and metabolic alterations in adipose tissue is not well established in human obesity. Human primary adipose tissue cells, including pre-adipocytes, endothelial cells and mature adipocytes, were used to investigate deregulation of cell-and pathway-specific gene profiles. Among factors known to alter adipose tissue biology, we focus on inflammatory (IL-1 beta and IL-17) and pro-fibrotic (TGF-beta 1) factors. rIL-1 beta and rIL-17 induced concordant pro-inflammatory transcriptional programs in pre-adipocytes and endothelial cells, with a markedly more potent effect of IL-1 beta than IL-17. None of these cytokines had significant effect on fibrogenesis-related gene expression, contrasting with rTGF-beta 1-induced up-regulation of extracellular matrix components and pro-fibrotic factors. In mature adipocytes, all three factors promoted down-regulation of genes functionally involved in lipid storage and release. IL-1 beta and IL-17 impacted adipocyte metabolic genes in relation with their respective pro-inflammatory capacity, while the effect of TGF-beta 1 occurred in face of an anti-inflammatory signature. These data revealed that IL-1 beta and IL-17 had virtually no effect on pro-fibrotic alterations but promote inflammation and metabolic dysfunction in human adipose tissue, with a prominent role for IL-1 beta.
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页数：11
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