Department of Infectious Disease, Imperial College London, Hammersmith Hospital, London, UK.
MRC Centre for Transplantation, Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, Great Maze Pond, London, SE1 9RT, UK.
BMC Biol. 2021 Nov 19;19(1):246. doi: 10.1186/s12915-021-01181-3.
Cell membrane fusion and multinucleation in macrophages are associated with physiologic homeostasis as well as disease. Osteoclasts are multinucleated macrophages that resorb bone through increased metabolic activity resulting from cell fusion. Fusion of macrophages also generates multinucleated giant cells (MGCs) in white adipose tissue (WAT) of obese individuals. For years, our knowledge of MGCs in WAT has been limited to their description as part of crown-like structures (CLS) surrounding damaged adipocytes. However, recent evidence indicates that these cells can phagocytose oversized lipid remnants, suggesting that, as in osteoclasts, cell fusion and multinucleation are required for specialized catabolic functions. We thus reason that WAT MGCs can be viewed as functionally analogous to osteoclasts and refer to them in this article as adipoclasts. We first review current knowledge on adipoclasts and their described functions. In view of recent advances in single cell genomics, we describe WAT macrophages from a 'fusion perspective' and speculate on the ontogeny of adipoclasts. Specifically, we highlight the role of CD9 and TREM2, two plasma membrane markers of lipid-associated macrophages in WAT, which have been previously described as regulators of fusion and multinucleation in osteoclasts and MGCs. Finally, we consider whether strategies aiming to target WAT macrophages can be more selectively directed against adipoclasts.
细胞膜融合和巨噬细胞多核化与生理稳态以及疾病都有关联。破骨细胞是多核的巨噬细胞，通过细胞融合导致代谢活性增加来吸收骨骼。巨噬细胞的融合也会在肥胖个体的白色脂肪组织（WAT）中产生多核巨细胞（MGC）。多年来，我们对 WAT 中的 MGC 的了解仅限于将其描述为围绕受损脂肪细胞的冠状结构（CLS）的一部分。然而，最近的证据表明，这些细胞可以吞噬过大的脂质残余物，这表明，与破骨细胞一样，细胞融合和多核化是专门的分解代谢功能所必需的。因此，我们认为 WAT MGC 可以被视为与破骨细胞功能类似，并在本文中将其称为脂肪破骨细胞。我们首先回顾了脂肪破骨细胞及其描述功能的现有知识。鉴于单细胞基因组学的最新进展，我们从“融合视角”描述了 WAT 中的巨噬细胞，并推测了脂肪破骨细胞的发生。具体来说，我们强调了 CD9 和 TREM2 的作用，这两个是 WAT 中与脂质相关的巨噬细胞的质膜标志物，它们以前被描述为破骨细胞和 MGC 中融合和多核化的调节剂。最后，我们考虑是否可以更有针对性地针对 WAT 巨噬细胞的靶向策略来靶向脂肪破骨细胞。
