期刊
CELL METABOLISM
卷 33, 期 2, 页码 270-+出版社
CELL PRESS
DOI: 10.1016/j.cmet.2020.11.008
关键词
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资金
- National Institutes of Health (NIH) [R01-DK111389, R37-AR046523, R01-AI123348, U19-AI142784, K08-AR065577, R01-AR070116, DP5 OD028125]
- Shriner's Hospital for Children grant [85400]
- Siteman Cancer Center
- Burroughs Wellcome Fund [CAMS 1019648]
- Children's Discovery Institute [MI-F-2019-795]
- Doris Duke Charitable Foundation
- Celgene Corporation
- Leo Pharma
- NCI Cancer Center Support grant [P30 CA91842]
- ICTS/CTSA grant from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1TR002345]
- NIH Roadmap for Medical Research
- [K99-HL138163]
Recent studies have shown that mitochondria can be transferred between cells to support metabolically compromised cells. In white adipose tissue (WAT), macrophages acquire mitochondria from neighboring adipocytes, defining a transcriptionally distinct subpopulation. This process is regulated by heparan sulfates (HS) and is impaired in obesity, leading to metabolic dysregulation.
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 sulfates (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 decreases 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 that regulates metabolic homeostasis and is impaired in obesity.
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