D-Dopachrome tautomerase promotes IL-6 expression and inhibits adipogenesis in preadipocytes
D-Dopachrome tautomerase promotes IL-6 expression and inhibits adipogenesis in preadipocytes
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DOI：
10.1016/j.cyto.2012.07.037
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发表时间：
2012-12-01
期刊：
影响因子：
3.8
通讯作者：
Yoshimoto, Katsuhiko
中科院分区：
文献类型：
--
作者：
Ishimoto, Kyoko;Iwata, Takeo;Yoshimoto, Katsuhiko
我们以前确定D-多巴色素互变异构酶（DDT）作为一种新的脂肪细胞因子，其mRNA水平在脂肪细胞中与肥胖相关的临床参数呈负相关，并作用于脂肪细胞来调节脂质代谢。本研究探讨DDT对前脂肪细胞的作用。重组DDT（rDDT）可增强人前脂肪细胞系SGBS细胞白细胞介素6（IL-6）的表达和分泌。rDDT处理增加磷酸化ERK 1/2的水平，但不是p38，在SGBS细胞，和rDDT诱导的IL-6 mRNA表达减弱预处理与ERK抑制剂，U 0126。敲低CD 74而非CD 44可抑制rDDT诱导的SGBS细胞IL-6 mRNA表达。这些结果表明，rDDT诱导前脂肪细胞表达IL-6是通过CD 74-ERK途径发生的。此外，在SGBS细胞进行成脂诱导，rDDT的三酰甘油的量减少，细胞与油滴的数量，和编码脂肪细胞标志物蛋白的mRNA的水平。在用rDDT处理的细胞中，脂肪形成过程中CCAAT/增强子结合蛋白家族和过氧化物酶体增殖物激活受体γ 2的表达增加受到抑制。这些结果提示DDT通过抑制前脂肪细胞成脂调控基因的表达而抑制脂肪细胞的形成。(C)2012爱思唯尔有限公司保留所有权利。
We previously identified D-dopachrome tautomerase (DDT) as a novel adipokine whose mRNA levels in adipocytes are negatively correlated with obesity-related clinical parameters, and which acts on adipocytes to regulate lipid metabolism. Here we investigated functions of DDT on preadipocytes. Recombinant DDT (rDDT) enhanced both the expression and secretion of interleukin-6 (IL-6) in SGBS cells, a human preadipocyte cell line. Treatment with rDDT increased levels of phosphorylated ERK1/2, but not p38, in SGBS cells, and rDDT-induced IL-6 mRNA expression was attenuated by pretreatment with an ERK inhibitor, U0126. Knockdown of CD74, but not CD44, inhibited rDDT-induced IL-6 mRNA expression in SGBS cells. These results suggested that the rDDT-induced IL-6 expression in preadipocytes occurred through the CD74-ERK pathway. Furthermore, in SGBS cells subjected to adipogenic induction, rDDT decreased the amount of triacylglycerol, number of cells with oil droplets, and levels of mRNA encoding adipocyte marker proteins. Increased expression of CCAAT/enhancer binding protein families and peroxisome proliferator-activated receptor gamma 2 during adipogenesis was inhibited in the cells treated with rDDT. These results suggested DDT to inhibit adipogenesis by suppressing the expression of genes encoding adipogenic regulators in preadipocytes. (C) 2012 Elsevier Ltd. All rights reserved.