Adipose tissue metabolism and CD11b expression on monocytes in obese hypertensives

Adipose tissue metabolism and CD11b expression on monocytes in obese hypertensives
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DOI:
10.1161/01.hyp.0000171477.63859.b2
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发表时间:
2005-07-01
期刊:
影响因子:
8.3
通讯作者:
Jordan, J
Jordan, J
中科院分区:
医学1区
文献类型:
--
作者:
Boschmann, M;Engeli, S;Jordan, J

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在一定程度的肥胖,代谢和心血管疾病的风险显着不同的个体。动物研究表明,单核细胞的差异表达的系统激活有助于肥胖相关的风险变异性。我们检验了系统性单核细胞活化与脂肪组织和骨骼肌代谢变化相关的假设。在17名肥胖高血压患者中,我们评估了循环单核细胞上的CD 11b表达,脂肪组织活检中的基因表达,并在空腹状态和葡萄糖负荷期间获得血液样本和脂肪组织以及骨骼肌微透析样本。将患者分为单核细胞上CD 11b表达较高和较低的组。在CD 11b表达较高的受试者的脂肪组织中,巨噬细胞标志物CD 68的表达显著增加。虽然两组间的全身胰岛素敏感性无差异,但外周CD 11b表达较高的患者在口服葡萄糖耐量试验期间脂肪组织中透析液葡萄糖显著增加,脂肪组织脂解也增加。我们的数据表明,人类单核细胞活化与葡萄糖和脂质代谢的组织特异性变化有关。这些发现可能部分由脂肪组织的单核细胞/巨噬细胞浸润解释,其似乎干扰胰岛素反应性。
At a given degree of adiposity, metabolic and cardiovascular risk varies markedly between individuals. Animal studies suggest that differentially expressed systemic activation of monocytes contributes to the obesity-associated risk variability. We tested the hypothesis that systemic monocyte activation is associated with changes in adipose tissue and skeletal muscle metabolism. In 17 obese hypertensive patients, we assessed CD11b expression on circulating monocytes, gene expression in adipose tissue biopsies, and obtained blood samples and adipose tissue and skeletal muscle microdialysis samples in the fasted state and during a glucose load. Patients were stratified into groups with higher and lower CD11b expression on monocytes. Expression of the macrophage marker CD68 was increased markedly in adipose tissue of subjects with higher CD11b expression. Although no differences in systemic insulin sensitivity were found between both groups, patients with higher peripheral CD11b expression showed a markedly augmented increase in dialysate glucose in adipose tissue during oral glucose tolerance testing and increased adipose tissue lipolysis as well. Our data demonstrate that human monocyte activation is associated with tissue-specific changes in glucose and lipid metabolism. These findings may be explained in part by monocyte/macrophage infiltration of adipose tissue, which appears to interfere with insulin responsiveness.