Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals.
Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals.
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DOI：
10.1016/j.cmet.2008.08.015
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发表时间：
2008-10
期刊：
影响因子：
29
通讯作者：
Neels JG
中科院分区：
文献类型：
--
作者：
Patsouris D;Li PP;Thapar D;Chapman J;Olefsky JM;Neels JG
肥胖脂肪组织的特征在于巨噬细胞的浸润。我们和其他人最近表明，一个特定的巨噬细胞亚群被招募到肥胖的脂肪和肌肉组织。该亚群表达CD11c并产生高水平的促炎细胞因子，这些促炎细胞因子与肥胖相关的胰岛素抵抗的发展有关。我们使用了一种条件性细胞消融系统，基于CD11c启动子控制下的白喉毒素受体的转基因表达，研究肥胖小鼠模型中CD11c+细胞耗竭的影响。我们的研究结果表明，CD11c+细胞耗竭导致胰岛素敏感性快速正常化。此外，CD11c+细胞消融导致局部和全身炎症标志物在基因表达水平和蛋白水平上显著降低。总之，这些结果表明这些CD11c+细胞是治疗肥胖相关胰岛素抵抗和II型糖尿病的潜在治疗靶点。
Obese adipose tissue is characterized by infiltration of macrophages. We and others recently showed that a specific subset of macrophages is recruited to obese adipose and muscle tissue. This subset expresses CD11c and produces high levels of pro-inflammatory cytokines that are linked to the development of obesity-associated insulin resistance. We used a conditional cell ablation system, based on transgenic expression of the diphtheria toxin receptor under the control of the CD11c promoter, to study the effects of depletion of CD11c+ cells in obese mouse models. Our results show that CD11c+ cell depletion results in rapid normalization of insulin sensitivity. Furthermore, CD11c+ cell ablation leads to a marked decrease in inflammatory markers, both locally and systemically, at the level of gene expression and protein levels. Together, these results indicate that these CD11c+ cells are a potential therapeutic target for treatment of obesity-related insulin resistance and type II diabetes.
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