期刊
CELL METABOLISM
卷 33, 期 3, 页码 547-+出版社
CELL PRESS
DOI: 10.1016/j.cmet.2020.12.001
关键词
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资金
- German National Academic Foundation, DFG [Fi2476/1-1]
- HFSP [LT000936/2020]
- DACH Gesellschaft fur Lipidologie
- DFG [HE3645/10-1, 335447727-SFB1328, SCHE522/4-1]
- BMBF [13XP5079C]
- Schering foundation
- Muhlbauer Stiftung
- Gertraud und Heinz Rose Stiftung
- UKE MD/PhD program
- Brown University startup fund
This study reveals that vascular endothelial cells in adipose tissues internalize significant amounts of triglyceride-rich lipoprotein particles under cold exposure which lead to enhanced proliferation of endothelial cells and adipocyte precursors, ultimately impacting thermogenic capacity through a β-oxidation-dependent mechanism.
In response to cold exposure, thermogenic adipocytes internalize large amounts of fatty acids after lipoprotein lipase-mediated hydrolysis of triglyceride-rich lipoproteins (TRL) in the capillary lumen of brown adipose tissue (BAT) and white adipose tissue (WAT). Here, we show that in cold-exposed mice, vascular endothelial cells in adipose tissues endocytose substantial amounts of entire TRL particles. These lipoproteins subsequently follow the endosomal-lysosomal pathway, where they undergo lysosomal acid lipase (LAL)-mediated processing. Endothelial cell-specific LAL deficiency results in impaired thermogenic capacity as a consequence of reduced recruitment of brown and brite/beige adipocytes. Mechanistically, TRL processing by LAL induces proliferation of endothelial cells and adipocyte precursors via beta-oxidation-dependent production of reactive oxygen species, which in turn stimulates hypoxia-inducible factor-1 alpha-dependent proliferative responses. In conclusion, this study demonstrates a physiological role for TRL particle uptake into BAT and WAT and establishes endothelial lipoprotein processing as an important determinant of adipose tissue remodeling during thermogenic adaptation.
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