Angiopoietin-2-integrin alpha 5 beta 1 signaling enhances vascular fatty acid transport and prevents ectopic lipid-induced insulin resistance

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Proper storage of excessive dietary fat into subcutaneous adipose tissue (SAT) prevents ectopic lipid deposition-induced insulin resistance, yet the underlying mechanism remains unclear. Here, we identify angiopoietin-2 (Angpt2)-integrin alpha 5 beta 1 signaling as an inducer of fat uptake specifically in SAT. Adipocyte-specific deletion of Angpt2 markedly reduced fatty acid uptake and storage in SAT, leading to ectopic lipid accumulation in glucose-consuming organs including skeletal muscle and liver and to systemic insulin resistance. Mechanistically, Angpt2 activated integrin alpha 5 beta 1 signaling in the endothelium and triggered fatty acid transport via CD36 and FATP3 into SAT. Genetic or pharmacological inhibition of the endothelial integrin alpha 5 beta 1 recapitulated adipocyte-specific Angpt2 knockout phenotypes. Our findings demonstrate the critical roles of Angpt2-integrin alpha 5 beta 1 signaling in SAT endothelium in regulating whole-body fat distribution for metabolic health and highlight adipocyte-endothelial crosstalk as a potential target for prevention of ectopic lipid deposition-induced lipotoxicity and insulin resistance. Fat uptake and storage in subcutaneous adipose tissue (SAT) prevents ectopic fat accumulation and associated metabolic complications, however, the underlying mechanisms are incompletely understood. Here, the authors show that adipose angiopoietin-2 (Angpt2) enhances SAT size via increased endothelial fatty acid transport.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2020-06
Language
English
Article Type
Article
Citation

NATURE COMMUNICATIONS, v.11, no.1

ISSN
2041-1723
DOI
10.1038/s41467-020-16795-4
URI
http://hdl.handle.net/10203/275603
Appears in Collection
MSE-Journal Papers(저널논문)
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