Targeted Deletion of Adipocytes by Apoptosis Leads to Adipose Tissue Recruitment of Alternatively Activated M2 Macrophages
Targeted Deletion of Adipocytes by Apoptosis Leads to Adipose Tissue Recruitment of Alternatively Activated M2 Macrophages
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DOI：
10.1210/en.2011-1031
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发表时间：
2011-08-01
期刊：
影响因子：
4.8
通讯作者：
Scherer, Philipp E.
中科院分区：
文献类型：
--
作者：
Fischer-Posovszky, Pamela;Wang, Qiong A.;Scherer, Philipp E.
肥胖通常与巨噬细胞浸润到脂肪组织中有关。脂肪细胞功能障碍导致巨噬细胞从交替激活的M2样表型向促炎性M1表型的表型转换。脂肪细胞和浸润性免疫细胞，特别是巨噬细胞之间的相互作用被认为有助于局部和最终全身炎症。在这里，我们测试了缺乏脂肪细胞对巨噬细胞炎症状态的表型影响。我们利用了通过靶向激活caspase-8（FAT-ATTAC）小鼠模型的脂肪凋亡，该模型允许通过促凋亡机制诱导脂肪细胞的全系统消除，并在消融活脂肪细胞后跟踪炎症反应的程度和类型。消除脂肪细胞后2周对贮库的分析导致脂肪组织水平显著降低，循环脂肪因子显著下调。附睾和腹股沟脂肪库的定量PCR和免疫组织化学显示巨噬细胞标志物F4/80和CD 11 c增加。使用多色流式细胞术，我们观察到在大多数F4/80阳性细胞上交替活化的M2巨噬细胞标志物（CD 206和CD 301）的上调。脂肪细胞的凋亡足以启动巨噬细胞大量流入残余脂肪垫。然而，这些巨噬细胞是交替活化的，是M2巨噬细胞而不是M1细胞。我们的结论是，脂肪细胞死亡是足以启动巨噬细胞浸润，和活的脂肪细胞需要启动和/或维持在脂肪组织中的浸润巨噬细胞内的促炎反应。（内分泌学152：3074-3081，2011）
Obesity is frequently associated with an infiltration of macrophages into adipose tissue. Adipocyte dysfunction causes a phenotypic switch of macrophages from an alternatively activated M2-like phenotype towards a proinflammatory M1 phenotype. The cross talk between adipocytes and infiltrating immune cells, in particular macrophages, is thought to contribute to local and eventually systemic inflammation. Here, we tested the phenotypic impact of a lack of adipocytes on the inflammatory status of macrophages. We took advantage of the fat apoptosis through targeted activation of caspase-8 (FAT-ATTAC) mouse model that allows for the inducible system-wide elimination of adipocytes through a proapoptotic mechanism and followed the degree and type of inflammatory response upon ablation of live adipocytes. Analysis of depots 2 wk after elimination of adipocytes resulted in markedly reduced levels of adipose tissue and a robust down-regulation of circulating adipokines. Quantitative PCR and immunohistochemistry on epididymal and inguinal fat depots revealed an increase of the macrophage markers F4/80 and CD11c. Using polychromatic flow cytometry, we observed an up-regulation of alternatively activated M2 macrophage markers (CD206 and CD301) on the majority of F4/80 positive cells. Apoptosis of adipocytes is sufficient to initiate a large influx of macrophages into the remnant fat pads. However, these macrophages are alternatively activated, antiinflammatory M2 macrophages and not M1 cells. We conclude that adipocyte death is sufficient to initiate macrophage infiltration, and live adipocytes are required to initiate and/or sustain a proinflammatory response within the infiltrating macrophages in adipose tissue. (Endocrinology 152: 3074-3081, 2011)