Patsouris David, Li Ping-Ping, Thapar Divya, Chapman Justin, Olefsky Jerrold M, Neels Jaap G
Division of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
Cell Metab. 2008 Oct;8(4):301-9. doi: 10.1016/j.cmet.2008.08.015.
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 proinflammatory cytokines that are linked to the development of obesity-associated insulin resistance. Here, 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, as reflected by 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.
肥胖的脂肪组织以巨噬细胞浸润为特征。我们和其他研究人员最近发现，有一类特定的巨噬细胞会被招募到肥胖的脂肪组织和肌肉组织中。这一亚群表达CD11c，并产生高水平的促炎细胞因子，这些细胞因子与肥胖相关的胰岛素抵抗的发展有关。在这里，我们使用了一种基于在CD11c启动子控制下白喉毒素受体转基因表达的条件性细胞消融系统，来研究在肥胖小鼠模型中耗竭CD11c+细胞的影响。我们的结果表明，CD11c+细胞耗竭会使胰岛素敏感性迅速恢复正常。此外，无论是在局部还是全身，CD11c+细胞消融都会导致炎症标志物显著减少，这在基因表达和蛋白质水平上都有体现。这些结果共同表明，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。
