Intercellular Mitochondria Transfer to Macrophages Regulates White Adipose Tissue Homeostasis and Is Impaired in Obesity.
Intercellular Mitochondria Transfer to Macrophages Regulates White Adipose Tissue Homeostasis and Is Impaired in Obesity.
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细胞间线粒体向巨噬细胞转移可调节白色脂肪组织稳态，并在肥胖症中受损。
DOI：
10.1016/j.cmet.2020.11.008
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发表时间：
2021-02-02
期刊：
影响因子：
29
通讯作者：
Teitelbaum SL
中科院分区：
文献类型：
--
作者：
Brestoff JR;Wilen CB;Moley JR;Li Y;Zou W;Malvin NP;Rowen MN;Saunders BT;Ma H;Mack MR;Hykes BL Jr;Balce DR;Orvedahl A;Williams JW;Rohatgi N;Wang X;McAllaster MR;Handley SA;Kim BS;Doench JG;Zinselmeyer BH;Diamond MS;Virgin HW;Gelman AE;Teitelbaum SL
最近的研究表明，线粒体可以在细胞之间转移，以支持代谢受损细胞的存活。然而，细胞间线粒体转移是否发生在白色脂肪组织（WAT）或调节体内代谢稳态仍然未知。我们发现巨噬细胞在体内从邻近的脂肪细胞获得线粒体，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敲除筛选揭示了线粒体摄取依赖于硫酸乙酰肝素（HS）。高脂饮食（HFD）诱导的肥胖小鼠在WAT巨噬细胞上表现出较低的HS水平和从脂肪细胞到巨噬细胞的细胞间线粒体转移减少。骨髓细胞中HS生物合成基因Ext 1的缺失减少了WAT巨噬细胞对线粒体的摄取，增加了WAT质量，降低了能量消耗，并加剧了体内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采用细胞间线粒体转移作为免疫代谢串扰的机制，以调节代谢稳态，这是在肥胖症受损。Brestoff等人表明，脂肪组织驻留的巨噬细胞在硫酸乙酰肝素依赖性过程中从邻近的脂肪细胞获得线粒体，该过程在肥胖症中受损。在小鼠中，巨噬细胞对线粒体摄取的遗传破坏降低了能量消耗并加剧了饮食诱导的肥胖，表明细胞间线粒体转移到巨噬细胞介导了全身代谢稳态。
Recent studies suggest that mitochondria can be transferred between cells to support the survival of metabolically compromised cells. However, whether intercellular mitochondria transfer occurs in white adipose tissue (WAT) or regulates metabolic homeostasis in vivo remains unknown. We found that macrophages acquire mitochondria from neighboring adipocytes in vivo and that this process defines a transcriptionally distinct macrophage subpopulation. A genome-wide CRISPR-Cas9 knockout screen revealed that mitochondria uptake depends on heparan sulfate (HS). High fat diet (HFD)-induced obese mice exhibit lower HS levels on WAT macrophages and decreased intercellular mitochondria transfer from adipocytes to macrophages. Deletion of the HS biosynthetic gene Ext1 in myeloid cells deceases mitochondria uptake by WAT macrophages, increases WAT mass, lowers energy expenditure, and exacerbates HFD-induced obesity in vivo. Collectively, this study suggests that adipocytes and macrophages employ intercellular mitochondria transfer as a mechanism of immunometabolic crosstalk to regulate metabolic homeostasis and that is impaired in obesity. Brestoff et al. show that adipose tissue-resident macrophages acquire mitochondria from neighboring adipocytes in a heparan sulfate-dependent process that is impaired in obesity. Genetic disruption of mitochondria uptake by macrophages reduces energy expenditure and exacerbates diet-induced obesity in mice, indicating that intercellular mitochondria transfer to macrophages mediates systemic metabolic homeostasis.
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作者：
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影响因子：
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作者：
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通讯作者：
Root, David E.
DOI：
10.1152/ajpendo.00277.2018
发表时间：
2019-02-01
影响因子：
5.1
作者：
Clemente-Postigo, Mercedes;Oliva-Olivera, Wilfredo;Tinahones, Francisco J.
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