Obesity induces a phenotypic switch in adipose tissue macrophage polarization
Obesity induces a phenotypic switch in adipose tissue macrophage polarization
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DOI：
10.1172/jci29881
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发表时间：
2007-01-01
影响因子：
15.9
通讯作者：
Saltiel, Alan R.
中科院分区：
文献类型：
--
作者：
Lumeng, Carey N.;Bodzin, Jennifer L.;Saltiel, Alan R.
脂肪组织巨噬细胞（ATMs）在肥胖期间浸润脂肪组织，并导致胰岛素抵抗。我们假设，高脂饮食时迁移到脂肪组织的巨噬细胞可能与正常饮食条件下驻留在那里的巨噬细胞不同。为此，我们在肥胖小鼠的脂肪组织中发现了一种新的F4/80(+)CD11c(+)的脂肪组织巨噬细胞群，而在瘦小鼠中未发现。瘦小鼠的脂肪组织巨噬细胞表达许多M2型或“选择性激活”巨噬细胞的特征基因，包括Ym1、精氨酸酶1和Il10。饮食诱导的肥胖降低了脂肪组织巨噬细胞中这些基因的表达，同时增加了诸如编码肿瘤坏死因子 -α和诱导型一氧化氮合酶等M1型或“经典激活”巨噬细胞特征基因的表达。有趣的是，来自肥胖的C - C趋化因子受体2基因敲除（Ccr2 - KO）小鼠的脂肪组织巨噬细胞表达M2标志物的水平与瘦小鼠相似。抗炎细胞因子白细胞介素 - 10在瘦小鼠的脂肪组织巨噬细胞中过表达，它保护脂肪细胞免受肿瘤坏死因子 -α诱导的胰岛素抵抗。因此，饮食诱导的肥胖导致脂肪组织巨噬细胞的激活状态从瘦动物中可能保护脂肪细胞免受炎症的M2极化状态转变为导致胰岛素抵抗的M1促炎状态。
Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80(+)CD11c(+) population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or "alternatively activated" macrophages, including Ym1, arginase 1, and Il10. Diet-induced obesity decreased expression of these genes in ATMs while increasing expression of genes such as those encoding TNF-alpha and iNOS that are characteristic of M1 or "classically activated" macrophages. Interestingly, ATMs from obese C-C motif chemokine receptor 2-KO (Ccr2-KO) mice express M2 markers at levels similar to those from lean mice. The antinflammatory cytokine IL-10, which was overexpressed in ATMs from lean mice, protected adipocytes from TNF-alpha-induced insulin resistance. Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance.