Obesity phenotype is related to NLRP3 inflammasome activity and immunological profile of visceral adipose tissue
Obesity phenotype is related to NLRP3 inflammasome activity and immunological profile of visceral adipose tissue
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DOI：
10.1007/s00125-013-3023-9
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发表时间：
2013-11-01
期刊：
影响因子：
8.2
通讯作者：
Paquot, Nicolas
中科院分区：
文献类型：
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作者：
Esser, Nathalie;L'homme, Laurent;Paquot, Nicolas
肥胖是一种异质性疾病，既包括保持代谢健康 (MHO) 的个体，也包括出现代谢紊乱（代谢不健康，MUO）的个体。脂肪组织也是异质的，因为其内脏成分比其皮下成分更频繁地与代谢功能障碍相关。代谢紊乱的发生部分是由 NLR 家族 Pyrin 结构域 3 (NLRP3) 炎症小体介导的，该炎症小体通过激活 caspase-1 增加炎症细胞因子的分泌。我们比较了 MUO 和 MHO 个体之间的免疫学特征和脂肪组织中的 NLRP3 活性。MHO 和 MUO 表型分别定义为代谢综合征的不存在和存在。通过流式细胞术、定量 RT-PCR 和组织培养研究，对 23 MUO、21 MHO 和 9 名瘦个体的皮下和内脏脂肪组织进行了细胞组成和内在炎症小体活性的研究。我们发现三个研究组之间存在显着差异，包括 IL-1 β 分泌增加、IL1B 和 NLRP3 表达增加、脂肪组织巨噬细胞数量增加以及内脏脂肪组织中调节性 T 细胞数量减少。 MUO 患者与 MHO 和瘦参与者进行比较。在内脏脂肪组织衍生的巨噬细胞中，MUO 患者的 caspase-1 活性和 IL-1 β 水平均高于 MHO 患者。此外，CD11c(+)CD206(+)脂肪组织巨噬细胞中的caspase-1活性高于CD11c(-)CD206(+)细胞。MUO表型似乎与浸润内脏脂肪组织的巨噬细胞中NLPR3炎症小体的激活增加有关，并且与MHO表型相比，炎症特征较差。
Obesity is a heterogeneous condition comprising both individuals who remain metabolically healthy (MHO) and those who develop metabolic disorders (metabolically unhealthy, MUO). Adipose tissue is also heterogeneous in that its visceral component is more frequently associated with metabolic dysfunction than its subcutaneous component. The development of metabolic disorders is partly mediated by the NLR family pyrin domain containing-3 (NLRP3) inflammasome, which increases the secretion of inflammatory cytokines via activation of caspase-1. We compared the immunological profile and NLRP3 activity in adipose tissue between MUO and MHO individuals.MHO and MUO phenotypes were defined, respectively, as the absence and the presence of the metabolic syndrome. Cellular composition and intrinsic inflammasome activity were investigated by flow cytometry, quantitative RT-PCR and tissue culture studies in subcutaneous and visceral adipose tissue from 23 MUO, 21 MHO and nine lean individuals.We found significant differences between the three study groups, including an increased secretion of IL-1 beta, increased expression of IL1B and NLRP3, increased number of adipose tissue macrophages and decreased number of regulatory T cells in the visceral adipose tissue of MUO patients compared with MHO and lean participants. In macrophages derived from visceral adipose tissue, both caspase-1 activity and IL-1 beta levels were higher in MUO patients than in MHO patients. Furthermore, caspase-1 activity was higher in CD11c(+)CD206(+) adipose tissue macrophages than in CD11c(-)CD206(+) cells.The MUO phenotype seems to be associated with an increased activation of the NLPR3 inflammasome in macrophages infiltrating visceral adipose tissue, and a less favourable inflammatory profile compared with the MHO phenotype.