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Publication : Multinucleated Giant Cells in Adipose Tissue Are Specialized in Adipocyte Degradation.

First Author  Braune J Year  2021
Journal  Diabetes Volume  70
Issue  2 Pages  538-548
PubMed ID  33158932 Mgi Jnum  J:307109
Mgi Id  MGI:6712889 Doi  10.2337/db20-0293
Citation  Braune J, et al. (2021) Multinucleated Giant Cells in Adipose Tissue Are Specialized in Adipocyte Degradation. Diabetes 70(2):538-548
abstractText  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 approximately 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-microm 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.
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