美国华盛顿大学医学院的Steven L. Teitelbaum团队发现，线粒体可被转移到巨噬细胞中，从而调节白色脂肪组织稳态，并且这种行为在肥胖中受损。这一研究成果于2020年12月4日在线发表在《细胞—代谢》上。

研究人员发现，巨噬细胞在体内从邻近的脂肪细胞中获取线粒体，并且该过程定义了转录上不同的巨噬细胞亚群。全基因组CRISPR-Cas9敲除筛选显示线粒体摄取取决于硫酸乙酰肝素（HS）。高脂饮食（HFD）诱导的肥胖小鼠在白色脂肪组织（WAT）巨噬细胞上表现出较低的HS水平，并且细胞间线粒体从脂肪细胞向巨噬细胞的转移减少。

髓样细胞中HS生物合成基因Ext1的缺失会降低WAT巨噬细胞对线粒体的摄取，增加WAT的质量，降低能量消耗，并加剧体内HFD诱导的肥胖。

总的来说，这项研究表明，脂肪细胞和巨噬细胞利用细胞间线粒体转移作为免疫代谢交流的一种机制，来调节代谢稳态并在肥胖症中受损。

研究人员介绍，最近的研究表明线粒体可以在细胞之间转移，从而支持代谢受损细胞的存活。然而，是否细胞间线粒体转移发生在WAT中或在体内调节代谢稳态仍是未知的。

附：英文原文

Title: Intercellular Mitochondria Transfer to Macrophages Regulates White Adipose Tissue Homeostasis and Is Impaired in Obesity

Author: Jonathan R. Brestoff, Craig B. Wilen, John R. Moley, Yongjia Li, Wei Zou, Nicole P. Malvin, Marina N. Rowen, Brian T. Saunders, Hongming Ma, Madison R. Mack, Barry L. Hykes, Dale R. Balce, Anthony Orvedahl, Jesse W. Williams, Nidhi Rohatgi, Xiaoyan Wang, Michael R. McAllaster, Scott A. Handley, Brian S. Kim, John G. Doench, Bernd H. Zinselmeyer, Michael S. Diamond, Herbert W. Virgin, Andrew E. Gelman, Steven L. Teitelbaum

Issue&Volume: 2020-12-04

Abstract: Recent studies suggest that mitochondria can be transferred between cells to supportthe survival of metabolically compromised cells. However, whether intercellular mitochondriatransfer occurs in white adipose tissue (WAT) or regulates metabolic homeostasis in vivo remains unknown. We found that macrophages acquire mitochondria from neighboringadipocytes in vivo and that this process defines a transcriptionally distinct macrophage subpopulation.A genome-wide CRISPR-Cas9 knockout screen revealed that mitochondria uptake dependson heparan sulfates (HS). High-fat diet (HFD)-induced obese mice exhibit lower HSlevels on WAT macrophages and decreased intercellular mitochondria transfer from adipocytesto macrophages. Deletion of the HS biosynthetic gene Ext1 in myeloid cells decreases mitochondria uptake by WAT macrophages, increases WATmass, lowers energy expenditure, and exacerbates HFD-induced obesity in vivo. Collectively, this study suggests that adipocytes and macrophages employ intercellularmitochondria transfer as a mechanism of immunometabolic crosstalk that regulates metabolichomeostasis and is impaired in obesity.

DOI: 10.1016/j.cmet.2020.11.008

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30603-3