Multinucleated Giant Cells in Adipose Tissue Are Specialized in Adipocyte Degradation
Multinucleated Giant Cells in Adipose Tissue Are Specialized in Adipocyte Degradation
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DOI：
10.2337/db20-0293
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发表时间：
2021-02-01
期刊：
影响因子：
7.7
通讯作者：
Gericke, Martin
中科院分区：
文献类型：
--
作者：
Braune, Julia;Lindhorst, Andreas;Gericke, Martin
肥胖与内脏脂肪组织（AT）的慢性低度炎症相关，其特征在于AT巨噬细胞（ATM）数量增加，并与2型糖尿病相关。AT炎症在组织学上由所谓的冠状结构的形成指示，因为ATM积聚在垂死的脂肪细胞周围，并且出现多核巨细胞（MGCs）。然而，迄今为止，MGCs在肥胖中的功能尚不清楚。因此，本研究的目的是表征AT中的MGCs并阐明这些细胞的功能。我们证明，MGCs发生在肥胖患者和高脂饮食24周后的小鼠中，伴随AT炎症的迹象，然后在小鼠中代表类似于3%的ATM。从机制上讲，我们发现了脂肪细胞死亡触发MGC形成的证据。最重要的是，肥胖AT中的MGCs具有更高的吞噬超大颗粒（如脂肪细胞）的能力，如AT的活体成像、离体45 μ m珠摄取和体内更高的脂质含量所示。最后，我们发现白细胞介素-4治疗足以增加AT中MGC的数量，而其他因素可能对体内内源性MGC的形成更重要。最重要的是，我们的数据表明，MGCs专门用于清除肥胖症中死亡的脂肪细胞。
Obesity is associated with chronic low-grade inflammation of visceral adipose tissue (AT) characterized by an increasing number of AT macrophages (ATMs) and linked to type 2 diabetes. AT inflammation is histologically indicated by the formation of so-called crown-like structures, as ATMs accumulate around dying adipocytes, and the occurrence of multinucleated giant cells (MGCs). However, to date, the function of MGCs in obesity is unknown. Therefore, the aim of this study was to characterize MGCs in AT and unravel the function of these cells. We demonstrated that MGCs occurred in obese patients and after 24 weeks of a high-fat diet in mice, accompanying signs of AT inflammation and then representing similar to 3% of ATMs in mice. Mechanistically, we found evidence that adipocyte death triggered MGC formation. Most importantly, MGCs in obese AT had a higher capacity to phagocytize oversized particles, such as adipocytes, as shown by live imaging of AT, 45-mu m bead uptake ex vivo, and higher lipid content in vivo. Finally, we showed that interleukin-4 treatment was sufficient to increase the number of MGCs in AT, whereas other factors may be more important for endogenous MGC formation in vivo. Most importantly, our data suggest that MGCs are specialized for clearance of dead adipocytes in obesity.