Interleukin-1β downregulates RBP4 secretion in human adipocytes.
Interleukin-1β downregulates RBP4 secretion in human adipocytes.
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DOI：
10.1371/journal.pone.0057796
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Fischer-Posovszky P
中科院分区：
文献类型：
--
作者：
Kotnik P;Keuper M;Wabitsch M;Fischer-Posovszky P
肥胖状态下脂肪组织的过度堆积与脂肪细胞分泌模式的改变、慢性低度炎症和代谢并发症有关。RBP4与这些改变有关，特别是胰岛素抵抗。本研究的目的是确定脂肪组织中的局部炎症微环境是否调节RBP4的表达和分泌。用人THP-1巨噬细胞条件培养液培养的人SGB和原代脂肪细胞作为脂肪炎症的体外模型。脂肪细胞暴露于重组肿瘤坏死因子-α、IL-1β、IL-6或IL-8。此外，还检测了18例健康女性脂肪组织中IL-1β和RBP4的共表达。用定量聚合酶链式反应和酶联免疫吸附试验检测RBP4的表达。在SGBs、脂肪细胞和人原代脂肪细胞中，与巨噬细胞条件培养液孵育后，RBP4mRNA的表达和分泌显着减少。在研究的几个因素中，我们确定IL-1β是一个新的调节RBP4的因子。IL-1β以时间和剂量依赖的方式显著下调RBP4mRNA和分泌。IL-1β通过IL-1受体和NF-κB介导其对RBP4表达的抑制作用，与IL-1受体阻断抗体共同孵育后，其抑制作用被NF-κB抑制剂CAPE和SC-514逆转。最有趣的是，皮下脂肪组织中β基因表达与IL-1基因表达呈负相关。肥胖状态下发现的脂肪组织炎症可能导致局部RBP4水平下调。IL-1β被认为是导致RBP4下降的主要因素。循环中RBP4的增加通常先于全身性胰岛素抵抗的发展，很可能与脂肪组织的炎症过程无关。
The excessive accumulation of adipose tissue in the obese state is linked to an altered secretion profile of adipocytes, chronic low-grade inflammation and metabolic complications. RBP4 has been implicated in these alterations, especially insulin resistance. The aim of the present study was to determine if a local inflammatory micro-environment in adipose tissue regulates RBP4 expression and secretion. Human SGBS and primary adipocytes cultured with conditioned media from human THP-1 macrophages were used as an in vitro model for adipose inflammation. Adipocytes were exposed to recombinant TNF-α, IL-1β, IL-6 or IL-8. In addition, coexpression of IL-1β and RBP4 was measured in adipose tissue samples from 18 healthy females. RBP4 expression was studied by quantitative PCR and ELISA. RBP4 mRNA expression and secretion was significantly reduced upon incubation with macrophage-conditioned media in SGBS adipocytes and human primary adipocytes. Out of several factors studied we identified IL-1β as a new factor regulating RBP4. IL-1β significantly downregulated RBP4 mRNA and secretion in a time- and dose-dependent manner. IL-1β mediated its inhibitory effects on RBP4 expression via IL-1 receptor and NF-κB, as incubation with the IL-1 receptor blocking antibody and the NF-κB inhibitors CAPE and SC-514 reversed its effect. Most interestingly, RBP4 mRNA was negatively correlated with IL-1β mRNA in subcutaneous adipose tissue. Adipose tissue inflammation as found in the obese state might lead to a downregulation in local RBP4 levels. IL-1β was identified as a major factor contributing to the decrease in RBP4. The increase in circulating RBP4 that often precedes the development of systemic insulin resistance is most likely unrelated to inflammatory processes in adipose tissue.
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炎症和代谢疾病中的脂肪因子。
DOI：
10.1038/nri2921
发表时间：
2011-02
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.1
作者：
Dinarello CA
通讯作者：
Dinarello CA
影响因子：
5.8
作者：
Levy-Marchal, Claire;Arslanian, Silva;Chiarelli, Francesco
通讯作者：
Chiarelli, Francesco
影响因子：
158.5
作者：
Graham, Timothy E.;Yang, Qin;Kahn, Barbara B.
通讯作者：
Kahn, Barbara B.
影响因子：
64.8
作者：
Yang, Q;Graham, TE;Kahn, BB
通讯作者：
Kahn, BB