Lysosomal lipoprotein processing in endothelial cells stimulates adipose tissue thermogenic adaptation
- Journal Article
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-1α-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. © 2020 Elsevier Show more
Journal / seriesCell Metabolism
Pages / Article No.
Subjectbrown adipose tissue; white adipose tissue; beige adipocytes; endothelial cells; lipoproteins; triglycerides; lysosomal acid lipase; angiogenesis; hypoxia-inducible factor 1α; thermogenesis
Organisational unit03819 - Wolfrum, Christian / Wolfrum, Christian
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