Stress augments insulin resistance and prothrombotic state: role of visceral adipose-derived monocyte chemoattractant protein-1.
Stress augments insulin resistance and prothrombotic state: role of visceral adipose-derived monocyte chemoattractant protein-1.
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DOI：
10.2337/db11-0828
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发表时间：
2012-06
期刊：
影响因子：
7.7
通讯作者：
Murohara T
中科院分区：
文献类型：
--
作者：
Uchida Y;Takeshita K;Yamamoto K;Kikuchi R;Nakayama T;Nomura M;Cheng XW;Egashira K;Matsushita T;Nakamura H;Murohara T
应激源导致血栓形成和胰岛素抵抗。由于肥胖相关的脂肪炎症也参与这些病理状态，我们假设压力与脂肪炎症相关。对雄性小鼠进行2周间歇性束缚应激。血脂、单核细胞/巨噬细胞标志物的表达（CD 11b、CD 68和F4/80），促炎细胞因子（单核细胞趋化蛋白-1 [MCP-1]、肿瘤坏死因子-α和白细胞介素-6）、脂联素、热休克蛋白70.1（HSP 70.1），和凝血因子采用免疫组织化学、酶联免疫吸附试验、免疫组织化学和免疫组织化学方法测定血液和腹股沟白色脂肪组织（WAT）中纤溶酶原激活抑制物-1（派-1）和组织因子（TF）的含量，和RT-PCR。通过葡萄糖耐量试验（GTT）和胰岛素耐量试验以及WAT中胰岛素受体底物-1（IRS-1）和葡萄糖转运蛋白4（GLUT 4）的表达来评估葡萄糖代谢。为了检查MCP-1阻断的效果，用对照或中和抗体处理动物，或用对照或7 ND（MCP-1的显性阴性形式）过表达的脂肪来源的基质细胞（ADSC）移植动物。应激增加单核细胞积累、游离脂肪酸、促炎细胞因子和HSP70.1，减少脂联素。脂肪基质细胞高表达MCP-1。应激引起的脂肪炎症增加派-1和TF，但不引起血栓形成。在GTT没有任何变化的情况下，应激使WAT的胰岛素敏感性恶化，IRS-1和GLUT 4降低。中和抗体和7 ND-ADSC逆转了应激诱导的脂肪炎症、促凝血状态和胰岛素抵抗。应激诱发脂肪炎症，通过脂肪来源的MCP-1增加凝血因子和损害胰岛素敏感性。
Stressors contribute to thrombosis and insulin resistance. Since obesity-related adipose inflammation is also involved in these pathological states, we assumed that stress correlates with adipose inflammation. Male mice were subjected to 2-week intermittent restraint stress. Expression of plasma lipids, monocyte/macrophage markers (CD11b, CD68, and F4/80), proinflammatory cytokines (monocyte chemoattractant protein-1 [MCP-1], tumor necrosis factor-α, and interleukin-6), adiponectin, heat shock protein 70.1 (HSP70.1), and coagulation factors (plasminogen activation inhibitor-1 [PAI-1] and tissue factor [TF]) in blood and inguinal white adipose tissue (WAT) was determined using immunohistochemistry, enzyme-linked immunosorbent assay, and RT-PCR, respectively. Glucose metabolism was assessed by glucose tolerance tests (GTTs) and insulin tolerance tests, and expression of insulin receptor substrate-1 (IRS-1) and glucose transporter 4 (GLUT4) in WAT. To examine effects of MCP-1 blockade, animals were treated with control or neutralizing antibody, or transplanted with control or 7ND (dominant-negative form of MCP-1)-overexpressing adipose-derived stromal cells (ADSCs). Stress increased monocyte accumulation, free fatty acids, proinflammatory cytokine, and HSP70.1 and reduced adiponectin. Adipose stromal cells highly expressed MCP-1. The stress-induced adipose inflammation increased PAI-1 and TF but did not give rise to thrombus formation. Without any changes in GTT, stress worsened insulin sensitivity and decreased IRS-1 and GLUT4 in WAT. Neutralizing antibody and 7ND-ADSCs reversed stress-induced adipose inflammation, procoagulant state, and insulin resistance. Stress evoked adipose inflammation to increase coagulation factors and impair insulin sensitivity through adipose-derived MCP-1.
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影响因子：
3
作者：
Benito, Manuel
通讯作者：
Benito, Manuel
肿瘤坏死因子-α的脂肪表达--在与肥胖相关的胰岛素抵抗中的直接作用
影响因子：
56.9
作者：
HOTAMISLIGIL, GS;SHARGILL, NS;SPIEGELMAN, BM
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Lodish, HF
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Dimsdale, Joel E.
影响因子：
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