Interleukin-6 mediates hepatic hypersecretion of apolipoprotein B.
Interleukin-6 mediates hepatic hypersecretion of apolipoprotein B.
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Interleukin-6 介导肝脏载脂蛋白 B 分泌过多。
DOI：
10.1152/ajpgi.00080.2010
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Sparks,CharlesE
中科院分区：
文献类型：
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作者：
Sparks,JanetD;Cianci,Joanne;Jokinen,Jenny;Chen,LiSheng;Sparks,CharlesE
肥胖和2型糖尿病与胰岛素抵抗（IR）、增加的循环促炎细胞因子和高脂血症相关，后者是由肝脏极低密度脂蛋白（VLDL）的过度产生引起的。一种与肝IR的发展密切相关的细胞因子是白细胞介素-6（IL-6）。我们的目的是评估IL-6对肝载脂蛋白B（apoB）和VLDL分泌的影响，并检查细胞因子信号传导和胰岛素抑制对脂蛋白分泌的影响之间可能存在的联系。在检查的细胞因子中，仅IL-6以剂量依赖性方式刺激含apoB的脂蛋白的分泌。在VLDL和密度>1.019 g/ml的脂蛋白中，B100和B48分泌均显著增加。在用IL-6处理的肝细胞中，胰岛素抑制肝apoB分泌的能力得以维持。脉冲追踪研究表明，增强apoB的合成是增加脂蛋白分泌的主要机制，这对应于较高丰度的apoB mRNA。由于IL-6没有改变apoB mRNA转录本的衰减速率，结果支持apoB mRNA水平的增加是apoB基因转录增强的结果。用制瘤素M（OSM）也检测到载脂蛋白B-脂蛋白分泌增加，支持信号转导蛋白gp 130的参与。细胞因子信号转导抑制因子（SOCS）3表达的增加否定了IL-6和OSM的作用，并显着降低细胞apoB mRNA丰度。我们的结论是IL-6通过改变载脂蛋白B基因转录增加载脂蛋白B的可用性，从而促进含载脂蛋白B的脂蛋白的分泌。这些变化可能导致与肥胖相关的VLDL分泌过多，特别是在SOCS 3没有过度表达到能够克服IL-6刺激的apob基因转录的程度的情况下。
Obesity and type 2 diabetes are associated with insulin resistance (IR), increased circulating proinflammatory cytokines, and hypertriglyceridemia, the latter being caused by overproduction of hepatic very low density lipoprotein (VLDL). One cytokine strongly linked with development of hepatic IR is interleukin-6 (IL-6). Our objective was to evaluate IL-6 effects on hepatic apolipoprotein B (apoB) and VLDL secretion and to examine possible linkages between cytokine signaling and insulin-suppressive effects on lipoprotein secretion. Of the cytokines examined, only IL-6 stimulated secretion of apoB-containing lipoproteins in a dose-dependent manner. Both B100 and B48 secretion were significantly increased in VLDL and in lipoproteins with a density >1.019 g/ml. The ability of insulin to suppress hepatic apoB secretion was maintained in hepatocytes treated with IL-6. Pulse-chase studies indicated that enhanced apoB synthesis was the primary mechanism for increased lipoprotein secretion, which corresponded with higher abundance of apoB mRNA. Because IL-6 did not alter the decay rate of apoB mRNA transcripts, results support that increased apoB mRNA levels are the result of enhancedapobgene transcription. Increased apoB-lipoprotein secretion was also detected with oncostatin M (OSM), supporting involvement of the signal-transducing protein, gp130. Increased suppressor of cytokine signaling (SOCS) 3 expression negated IL-6 and OSM effects and significantly reduced cellular apoB mRNA abundance. We conclude that IL-6 favors secretion of apoB-containing lipoproteins by increasing availability of apoB through changes inapobgene transcription. These changes may contribute to hypersecretion of VLDL associated with obesity, particularly under conditions where SOCS3 is not overexpressed to an extent capable of overcoming IL-6-stimulatedapobgene transcription.